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Review

The Role of LncRNAs in Translation

by
Didem Karakas
1 and
Bulent Ozpolat
2,*
1
Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Istinye University, Istanbul 34010, Turkey
2
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Non-Coding RNA 2021, 7(1), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010016
Submission received: 4 January 2021 / Revised: 16 February 2021 / Accepted: 18 February 2021 / Published: 20 February 2021
(This article belongs to the Special Issue Post-transcriptional Regulation through Long Non-coding RNAs (lncRNAs))
Browse Figures
Versions Notes

Abstract

:
Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Depending on cellular location, lncRNAs are involved in a wide range of cellular functions, including chromatin modification, transcriptional activation, transcriptional interference, scaffolding and regulation of translational machinery. This review highlights recent studies on lncRNAs in the regulation of protein translation by modulating the translational factors (i.e, eIF4E, eIF4G, eIF4A, 4E-BP1, eEF5A) and signaling pathways involved in this process as wells as their potential roles as tumor suppressors or tumor promoters.

1. Introduction

The majority of the mammalian genome consists of non-coding RNAs (ncRNAs), including long ncRNAs (lncRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and small ncRNAs such as microRNAs (miRNAs), small nuclear RNAs (snRNA) and circular RNAs (circRNAs), while only a small portion (~1.5%) of it is comprised of protein-coding mRNAs [1].
lncRNA transcripts, which are a group of ncRNAs longer than 200 nucleotides, account for the majority (98%) of the ncRNAs. Currently, about 30,000 different lncRNA transcripts are belived to exist in the human genome [2]. Since most lncRNAs are transcribed by RNA polymerase II (RNAP II), they share some similarities with mRNAs, such as poly-adenylation and the presence of 5′-cap structure. Just like mRNAs, lncRNAs form secondary structures, undergo post-transcriptional processing (i.e., 5’-cap structure, polyadenylation) and splicing [3], present in the nucleus, cytosol, and mitochondria [4], and can have tissue-specific expression patterns.
lncRNAs have been shown to play a pivotal role in a wide range of cellular processes such as gene expression, translation regulation, splicing, chromosomal organization and X chromosome silencing [5,6,7]. Besides, specific lncRNAs are known to be dysregulated in various diseases, such as cancer, neurological diseases, and diabetes [8]. Considering their extensive roles in both health and disease, a better understanding of the functions of lncRNAs in the regulation of cellular events is needed.
In this review, we aim to discuss the role of lncRNAs in the regulation of protein translation by controlling translational factors and signaling pathways. Furthermore, because translational regulation is often dysregulated in cancer cells, we also briefly summarize the role of lncRNAs in tumorigenesis and cancer progression as tumor promoters or tumor suppressors.

2. An Overview of the Characteristics of LncRNAs

Although lncRNAs were initially assumed as transcriptional noise or genomic “junk” [9,10], studies later revealed that they play vital roles in the regulation of various cellular processes, such as cell division, proliferation, differentiation, cell cycle, cell death, and metabolism [11,12,13,14,15]. Recent reports indicated some lncRNAs have a small open-reading frame (sORFs/smORFs) and are associated with ribosomes, suggesting their protein-coding potential [16,17,18,19,20]. In fact, recent studies showed that a small number of lncRNAs are capable of encoding small proteins called micropeptides (less than 100 amino acids) that are involved in the regulation of various biological processes [21].
Initial studies suggested that lncRNAs were thought of as unstable transcripts. However, later studies demonstrated that the majority of 800 lncRNAs have half-lives greater than 16 h and are highly stable, while only a minority of lncRNAs have half-lives less than 2 h [22].
lncRNAs have been traditionally categorized according to their specific locations on the genome into five major groups, including antisense, sense, bidirectional, intronic, and intergenic RNAs [23]. In a recent report, a more detailed classification has been proposed to describe the diversity of lncRNAs. This new classification includes seven different groups of lncRNAs: (a) mRNA-like intergenic transcripts (lincRNAs), (b) anti-sense transcripts of protein coding genes (natural anti-sense transcripts -NATs-), (c) processed transcripts, (d) enhancer RNAs (eRNAs), (e) promoter upstream transcripts (PROMPTs), (f) small nucleolar RNA (snoRNA)-ended lncRNAs (sno-lncRNAs), and (g) circular intronic RNAs (ciRNAs) [24].

3. Regulatory Functions of LncRNAs Depending on Their Subcellular Location

Since lncRNAs are capable of interacting with nucleic acids (DNA, RNA) and proteins, they are involved in the regulation of diverse molecular processes such as epigenetic and (post)-transcriptional modifications, translational regulation, splicing and scaffolding [6,7,25]. These diverse functions of lncRNAs are closely associated with their cellular location. lncRNAs are predominantly found in the nucleus and cytoplasm [1], while some lncRNA transcripts can be localized in exosomes. Recent findings revealed that large quantities of lncRNAs are exported to the cytoplasm to display their vital regulatory functions in cytoplasmic processes [19,26,27]. Subcellular localization of lncRNAs is a tightly regulated process controlled by various factors, such as sequence and structural motifs [28].
Based on their location in the cell, lncRNAs are involved in different molecular processes. The nuclear lncRNAs are closely associated with chromatin structures and regulate gene expression by influencing diverse mechanisms such as transcriptional and epigenetic regulation of specific genes and pre-mRNA processing [29]. In contrast, cytoplasmic lncRNAs dominantly control the stability and translation of mRNAs [27]. For instance, lncRNAs such as MALAT1 and NEAT1 are predominantly found in the nucleus; DANCR and OIP5-AS1 are found mainly in the cytoplasm; TUG1, CasC7 and HOTAIR have both nuclear and cytoplasmic distribution [30]. Since the subcellular location determines the function of lncRNAs, in this section, we aim to highlight the regulatory functions of lncRNAs depending on their subcellular locations.

3.1. Cytoplasmic LncRNAs

Cytoplasmic lncRNAs control a wide range of cellular processes by interacting with miRNAs, mRNAs and proteins. They can reciprocally interact with miRNAs and affect the functions of miRNAs in various ways. lncRNAs can function as competing endogenous RNAs (ceRNA) to bind miRNAs and block miRNA-mRNA interactions. For instance, BACE1 (beta-secretase-1) mRNA expression has been shown to be inhibited by miR-485-5p [31]. BACE1-antisense lncRNA and miR-485-5p compete for the same binding site in the ORF of the BACE1 mRNA and BACE1-antisense lncRNA prevents the mRNA-miRNA interaction [31]. In the second mechanism of lncRNA-miRNA interaction, lncRNAs can act as miRNA sponges or decoys and attract miRNAs, competitively sequestering miRNAs away from the target mRNAs [32]. For instance, lncRNA GAS5 (Growth arrest-specific 5), a tumor suppressor, functions as a sponge by sequestering and decreasing oncogenic effects of miR-21 and inhibits the proliferation of cancer cells and induces apoptotic cell death [33,34]. Similarly, lncRNA TRPM2-AS acts as a sponge or a competitive endogenous RNA for tumor-suppressor miR-612 and consequently modulates the derepression of IGF2BP1 and FOXM1 [35]. Silencing of TRPM2-AS inhibited aggressiveness of tumors in gastric cancer patients (proliferation, metastasis, radioresistance), while its overexpression promoted progression of gastric cancer [35].
lncRNAs in cytoplasm are also involved in the modulation of turnover and translation of some specific mRNAs [27]. lncRNAs can prevent the formation of mRNA-miRNA complexes as abovementioned, or they can bind to RNA-binding proteins (RBPs) [36,37]. For instance, lncRNA LAST stabilizes mRNA levels of Cyclin D1 (CCND1) oncogene. lncRNA LAST promotes the binding of CNBP-RBP (CCHC-type zinc finger nucleic acid binding protein) to CCND1, resulting in increased expression of CCND1 by stabilizing its mRNA [38]. Morover, lncRNAs modulate protein stability by influencing to enhance or hinder access to the ubiquitin-dependent proteasomal degradation machinery [27]. A study showed that lncRNA-p21 levels were transcriptionally activated by HIF-1α (Hypoxia-inducible factor-1α) under hypoxic conditions, then lncRNA-p21 binds to both HIF-1α and VHL (von Hippel-Lindau) proteins to protect HIF-1α from VHL-mediated ubiquitination [39]. Furthermore, lncRNAs can promote the proteasomal degradation. For instance, lnc-β-Catm recruits EZH2 to catalyze K49 methylation of β-catenin which inhibits phosphorylation and ubiquitination of β-catenin and promotes its stability [40].

3.2. Nuclear LncRNAs

Some of the lncRNAs are located in the nucleus to regulate gene expression by modulating chromatin organization, RNA processing and transcription [41,42,43,44,45]. The modulatory roles of lncRNAs on gene expression can be either cis- or trans-acting [41] and could negatively or positively affect the expression of target gene.

4. Acting Mechanisms of LncRNAs in the Regulation of Translation

4.1. Overview of Protein Translation Process

Protein translation is a highly complex process, comprising three steps (initiation, elongation, translation) and each step requires dynamic and efficient interactions between a great number of proteins, RNAs and ribosome.
The initiation process consists of two main steps. The first step involves the formation of the pre-initiation complex, and the second step is the assembling of this complex to the large subunit of the ribosome [46]. The initiation step begins with the formation of a ternary complex (eIF2-GTP-Met-tRNA), then the complex binds to small subunit (40S) of ribosome and assembles a pre-initiation complex by binding to other initiation factors (eIF1, eIF1A, eIF3, and eIF5) [47,48]. Before the pre-initiation complex directs to the 5′ end of mRNA, eIF4F complex, which is formed by eIF4E (cap-binding protein), eIF4G (scaffold protein) and eIF4A (helicase), bind to the 5′ end of mRNA to unwind and activate it [46,49]. The formation of eIF4F complex is maintained by some other initiation factors, eIF4B and eIF3. The pre-initiation complex then scans the mRNA until it recognizes a start codon [50]. Once the start codon is recognized, eIF5 and eIF5B promote hydrolysis of eIF2-bound GTP, releasing of eIFs from the complex and joining to the large subunit of the ribosome [51]. Following the initiation step of translation, met-tRNA reaches the P (peptidyl)-site of the 80S ribosome awaiting amino acids for elongation of the peptide chain.
The elongation step of translation requires the recruitment of aminoacyl-tRNA to the A (aminoacyl)-site of ribosome through GTP-bound eukaryotic elongation factor 1A (eEF1A). Although there is no base-pairing between tRNA anticodon and A-site codon, tRNA generates a codon-anticodon helix by remodeling itself [52] and stabilizes the ternary complex (aa-tRNA-eIF1A-GTP) [53]. Base-pairing interactions between A-site codon and aa-tRNA anticodon induce hydrolysis of GTP by eEF1A, which is then released from the A-site of the ribosome. eEF1A-GDP complex is recycled by eEF1B. Following the transfer of aa-tRNA to the A-site, a conformational change occurs in the ribosome which facilitates the formation of peptide bond between the aa-tRNA and the tRNA carrying the Met-tRNA at the P site. A GTPase (eEF2) binds to the A-site of the ribosome, hydrolyzes GTP and stimulates a conformational change in the ribosome resulting in movement of the ribosome one codon further. After the translocation of the ribosome, the A-site becomes empty and can accept the next aa-tRNAs to start a new cycle of elongation [52].
The last step of protein translation is termination, which begins when a stop codon (UAA, UGA, or UAG) reaches the A-site of the ribosome. Two types of release factors, eRF1 and eRF3, are involved in the termination process [54,55,56]. eRF1 is responsible for the recognition of stop codon and stimulation of peptide release, while eRF3 binds to eRF1 and triggers eRF1-mediated peptide release via GTPase activity [56,57]. The ternary complex (eRF1-eRF3-GTP) then binds to the ribosomal pre-termination complex and eRF3 hydrolyses GTP to release polypeptide [58].

4.2. Regulation of Translational Factors by LncRNAs

4.2.1. Inhibitory Roles of LncRNAs in Translation through Regulation of Translation Factors

A growing body of evidence demonstrates that lncRNAs can regulate each step of translation by regulating the expression and the function of translation factors. For instance, lncRNA GAS5 is involved in the regulation of apoptosis and cell proliferation. A study performed with lymphoma cells showed that GAS5 interacts with the translation initiation complex, eIF4F, by directly binding to eIF4E and decreasing the translation of c-Myc [37]. Similarly, lncRNA RP1-5O6.5 has been shown to interact with eIF4E and prevents binding of eIF4E to eIF4G, leading to inhibition of translation of p27kip1, which negatively regulates Snail levels in breast cancer cells [59]. lncRNAs SNHG1 and SNGH4 are capable of binding to eIF4E and dysregulate the function of eIF4E in mantle cell lymphoma cells [60]. In the other example, lncRNA treRNA has been shown to interact with ribonucleoproteins (RNPs) (hnRNP K, FXR1, FXR2, PUF60, and SF3B3) and form treRNA-RNP complex which suppresses the translation efficiency of E-cadherin by binding eIF4G1 [61]. A brain-specific lncRNA, BC1, has been reported to interact with eIF4A and poly(A)-binding protein (PABP) and negatively regulate translation process [62,63]. lncRNA GAPLINC is overexpressed in non-small lung cancer cells and it increases eEF2K expression (a negative regulator of eEF2) by acting as a sponge for miR-661 [64]. In the other study, lncRNA FOXD1-AS1 was shown to bind to eIF5A, however it did not change the mRNA expression levels, suggesting that FOXD1-AS1 can involve in the post-translational regulation [65]. Overall, these studies suggested that lncRNAs can play an important inhibitory roles in mRNA translation through regulation of translation factors.

4.2.2. LncRNAs Positively Regulate Protein Translation

Some lncRNAs have been reported to positively regulate protein translation. For instance, lncRNA SRA enhanced Wnt/β-catenin signaling pathway by increasing the expression of eIF4E-binding protein 1 (eIF4E-BP1) and contributed to the aggressive characteristics of endometrial cancer [66]. Another study showed that lncRNA MCM3AP-AS1 enhances the expression of eIF4E by acting as a sponge for miR15a, which supresses eIF4E expression and contributes to doxorubicin resistance in Burkitt lymphoma cells through MCM3AP-AS1/miR-15a/eIF4E axis [67]. Similarly, lncRNA SNHG12 enhanced the invasion of human vascular smooth muscle cells by serving as a sponge of miR-766-5p and influencing the miR-766-5p/eIF5A axis [68]. In the other study, a Y-linked lncRNA, LINC00278, was found to encode a micropeptide called YY1BM which led to a decrease in the expression of negative regulator of translation, eEF2K [69]. The functions of lncRNAs on translational factors are summarized in Table 1.

4.3. LncRNAs Involved in Signaling Pathways Regulating Protein Translation

The PI3K/AKT/mTOR is one of the major signaling pathways known to regulate vital cellular processes including cell proliferation, growth, survival, metabolism and protein translation. The role of PI3K/AKT/mTOR and MAPK pathways in the regulation of translational machinery are well documented and they are frequently overactivated in most types of cancer [70]. Both pathways involve the mechanistic target of rapamycin (mTOR) to regulate a variety of components of the translational machinery in homeostasis, their dysregulation results in aberrant translation which is often detected in diabetes, neurological disorders, and cancer [71,72,73,74]. The MAPK family consists of a serine/threonine kinases, that includes ERKs, JNKs and p38/SAPKs [75]. Especially the MAPK/ERK signaling pathway is amongst the most well-studied, signaling and dysregulating one-third of all human cancers [76].
PI3K/AKT/mTOR pathway regulates cell growth and proliferation by phosphorylating two downstream targets which are 4E-BP1 and ribosomal protein S6 kinase (S6Ks). mTOR complex I (mTORC1) controls translational activation by phosphorylating eIF4E inhibitor, 4E-BP1, which releases eIF4E to interact with initiation complex (eIF4F) [77]. S6K protein requires sequential phosphorylations at multiple serine/threonine sites and mTORC1 regulates its activation by phosphorylation. Once S6K is activated, it phosphorylates and activates eIF4B, which increases the recruitment of eIF4B to eEF4A and enhances translation [78]. Besides, S6K and mTORC1 signaling pathways can phosphorylate EF2-Kinase (EF2K) and decrease its sensitivity to Ca/Calmoduline for its activation [79]. Similarly, eEF2K activity is negatively regulated by MAPKs and their downstream effectors, reducing phosphorylation of eEF2, leading to increased translation by promoting peptide elongation phase of protein systhesis [80,81]. Considering the significant regulatory roles of PI3K/AKT/mTOR and MAPK signaling pathways in protein translation, regulation of their activity by lncRNAs indicate that the lncRNAs are involved in controlling protein translation through regulation of these key signaling pathways. For instance, lncRNA UASR1 promotes cell growth and migration of breast cancer cells by regulating AKT/mTOR pathway [82]. In these cells, active mediators of this pathway such as p-AKT, p-TSC2, p-4EBP1 and p-p70S6K are increased by overexpression of UASR1. Thus, UASR1 plays an oncogenic role in breast cancer cells through activation of the AKT/mTOR signaling pathway. Another lncRNA H19 is overexpressed in colorectal cancer tissues and it promotes the activity of PI3K/AKT pathway by acting as a ceRNA and regulating some components of this pathway. H19 regulates various cancer-related mRNAs (such as (AKT3, CSF1, MET, COL1A1) by competitively sponging various miRNAs. Knockdown of H19 reduced protein level of MET, ZEB1, and COL1A1 in vitro [83]. The other study showed that H19 inhibits mTORC1-mediated 4E-BP1 phosphorylation, but it does not affect the activation of S6K1 [84]. lncRNA CASC9 has been shown to suppress apoptosis and promote aggressiveness of oral squamous cell carcinoma cells by activating the AKT/mTOR pathway [85].
In contrast, some lncRNAs might negatively regulate the abovementioned pathways. For instance, lncRNA FER1L4 suppresses cell proliferation and metastasis through downregulating the expressions of PI3K and AKT in lung cancer cells [86]. Overall, lncRNAs can regulate signaling pathways involved in translational control that is an integral part of these survival adaptive pathways in normal and cancer cells. Some of these regulatory lncRNAs and their functions on signaling pathways are summarized in Table 2.

4.4. LncRNAs in Cancer

4.4.1. LncRNAs Can Contribute Hallmarks of Cancer

Deregulation of mRNA translation is commonly observed in malignant cells and is considered as a critical factor contributing to cancer initiation, tumorigenesis, and progression. Because lncRNAs play critical roles in the regulation of a wide range of cellular processes, their dysregulation is associated with cell proliferation, survival, tumorigenesis and progression of various cancers, and aberrant expression of lncRNAs can contribute to the hallmarks of cancer. Reprograming of the translation machinery in cancer cells is important function of the key oncogenic signalings, promoting cellular transformation. Increased activity of translational machinery has been shown to be critical in many cancer cells, including breast [97], pancreatic [98], liver [99], and colorectal cancer [100], and leukemia [101]. Thus, lncRNA-mediated regulation of protein translation plays an important role in promoting oncogenic signaling, and specific targeting of these lncRNAs holds promise for developing highly targeted therapies in cancer and other human diseases. Figure 1 illustrates some of the lncRNAs that are involved in tumorigenesis and cancer progression.

4.4.2. The Functions of LncRNAs in Regulating Translation of Cancer-Related Proteins

As mentioned above, various lncRNAs are involved in the regulation of hallmarks of cancer, suggesting that they have potential regulatory roles in cancer-related protein tranlation. Since we have already summarized the roles of some lncRNAs on PI3K/AKT/mTOR and MAPK pathways in Table 2, here we briefly focus on the interaction between lncRNAs and translation, promoting the aggressive tumor characteristics.
An example of a lncRNA that is well-known to be associated with cancer is MALAT1. MALAT1 was shown to upregulate the expression of glycolytic genes which contributes the aggressive characteristics of hepatocellular carcinoma cells. MALAT1 regulated the glucose metabolism of hepatocellular carcinoma cells by enhancing translation of metabolic transcription factor TCF7L2 through mTORC1–4EBP1 axis [87]. lncRNA NEAT1 represents another example of lncRNAs that contribute to the aggressiveness of non-small cell lung cancer by enhancing eIF4G2 via miR-582-5p sponging effects [148]. Similarly, lncRNA RP11-284P20.2 enhanced c-met mRNA translation by recruiting eIF3b to c-met and thus promoted proliferation and invasion of hepatocellular carcinoma cells [149]. In prostate cancer, lncRNA UCA1 levels were found to be positively correlated with eIF4G1 levels. UCA1 enhances eIF4G1 levels via sponging miR-331-3p, while knockingdown of UCA1 sensitizes prostate cancer cells to radiotherapy by suppressing eIF4G1 expression via miR-331-3p/eIF4G1 axis [150]. In another study, lncRNA GAPLINC increased the eEF2K expression by serving as a sponge for miR-661, thereby promoted proliferation and progression of non-small cell lung cancer [64].
lncRNAs can also regulate translation process by interacting with the ribosome or ribosome-related proteins. For example, lncRNA ZFAS1 was shown to interact with a small 40S subunit of the ribosome in breast cancer cells. The study showed that ZFAS1 did not regulate translation process directly. Instead, the lncRNA was increased during the ribosome biogenesis indicating its role in regulating the ribosome production and assembly [151]. In neuroblastoma cells, it was shown that lncNB1 enhanced E2F1 protein synthesis and N-Myc stability by binding the ribosomal protein RPL35 [152].
Overall, an emerging body of evidence suggests that lncRNAs play important roles in the regulation of protein translation process. They can enhance or suppress translation via several mechanisms, including through interacting with the ribosome-associated proteins, sponging miRNAs, and competing with endogenous RNAs. Their mechanisms of action and some examples are summarized in Figure 2.

5. Conclusions

Advances in high throughput technologies resulted in the identification of a large number of lncRNAs. Although thousands of lncRNAs have been identified in the genomes of higher eukaryotes, our understanding of the mechanisms by which lncRNAs exert their precise function for most of them remains unknown. Elucidating the function of these lncRNAs is expected to provide deeper insight into the molecular mechanisms regarding their function in human diseases, including cancer and the interaction of lncRNAs with other molecules may help to design novel strategies. Accumulating evidence indicates that lncRNAs display pivotal roles in the regulation of almost every cellular process by binding to the target proteins, mRNAs, miRNA, and/or DNAs, indicating the complicated roles of lncRNAs. Recent findings revealed that lncRNAs can play important roles in the pathogenesis of human cancers, contributing to tumor growth and progression. Thefore, a better understanding of the role of lncRNAs is needed to elucidate the missing links in the molecular mechanims involved in human diseases, including cancer.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Derrien, T.; Johnson, R.; Bussotti, G.; Tanzer, A.; Djebali, S.; Tilgner, H.; Guernec, G.; Martin, D.; Merkel, A.; Knowles, D.G.; et al. The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Res. 2012, 22, 1775–1789. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Rinn, J.L.; Chang, H.Y. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 2012, 81, 145–166. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Quinn, J.J.; Chang, H.Y. Unique features of long non-coding RNA biogenesis and function. Nat. Rev. Genet. 2016, 17, 47–62. [Google Scholar] [CrossRef] [PubMed]
  4. Aillaud, M.; Schulte, L.N. Emerging Roles of Long Noncoding RNAs in the Cytoplasmic Milieu. ncRNA 2020, 6, 44. [Google Scholar] [CrossRef] [PubMed]
  5. Penny, G.D.; Kay, G.F.; Sheardown, S.A.; Rastan, S.; Brockdorff, N. Requirement for Xist in X chromosome inactivation. Nature 1996, 379, 131–137. [Google Scholar] [CrossRef] [PubMed]
  6. Böhmdorfer, G.; Wierzbicki, A.T. Control of Chromatin Structure by Long Noncoding RNA. Trends Cell Biol. 2015, 25, 623–632. [Google Scholar] [CrossRef] [Green Version]
  7. Connerty, P.; Lock, R.B.; de Bock, C.E. Long Non-coding RNAs: Major Regulators of Cell Stress in Cancer. Front. Oncol. 2020, 10, 285. [Google Scholar] [CrossRef] [Green Version]
  8. DiStefano, J.K. The Emerging Role of Long Noncoding RNAs in Human Disease. Methods Mol. Biol. 2018, 1706, 91–110. [Google Scholar] [PubMed]
  9. Ponjavic, J.; Ponting, C.P.; Lunter, G. Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Res. 2007, 17, 556–565. [Google Scholar] [CrossRef] [Green Version]
  10. Struhl, K. Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nat. Struct. Mol. Biol. 2007, 14, 103–105. [Google Scholar] [CrossRef]
  11. Guttman, M.; Amit, I.; Garber, M.; French, C.; Lin, M.F.; Feldser, D.; Huarte, M.; Zuk, O.; Carey, B.W.; Cassady, J.P.; et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 2009, 458, 223–227. [Google Scholar] [CrossRef]
  12. Guttman, M.; Donaghey, J.; Carey, B.W.; Garber, M.; Grenier, J.K.; Munson, G.; Young, G.; Lucas, A.B.; Ach, R.; Bruhn, L.; et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 2011, 477, 295–300. [Google Scholar] [CrossRef] [Green Version]
  13. Hung, T.; Wang, Y.; Lin, M.F.; Koegel, A.K.; Kotake, Y.; Grant, G.D.; Horlings, H.M.; Shah, N.; Umbricht, C.; Wang, P.; et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat. Genet. 2011, 43, 621–629. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Rossi, M.N.; Antonangeli, F. LncRNAs: New Players in Apoptosis Control. Int. J. Cell Biol. 2014, 2014, 473857. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Lin, Y.H. Crosstalk of lncRNA and Cellular Metabolism and Their Regulatory Mechanism in Cancer. Int. J. Mol. Sci. 2020, 21, 2947. [Google Scholar] [CrossRef] [PubMed]
  16. Chew, G.L.; Pauli, A.; Rinn, J.L.; Regev, A.; Schier, A.F.; Valen, E. Ribosome profiling reveals resemblance between long non-coding RNAs and 5′ leaders of coding RNAs. Development 2013, 140, 2828–2834. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Aspden, J.L.; Eyre-Walker, Y.C.; Phillips, R.J.; Amin, U.; Mumtaz, M.A.; Brocard, M.; Couso, J.P. Extensive translation of small Open Reading Frames revealed by Poly-Ribo-Seq. eLife 2014, 3, e03528. [Google Scholar] [CrossRef] [PubMed]
  18. Ruiz-Orera, J.; Messeguer, X.; Subirana, J.A.; Alba, M.M. Long noncoding RNAs as a source of new peptides. eLife 2014, 3, e03523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  19. Van Heesch, S.; van Iterson, M.; Jacobi, J.; Boymans, S.; Essers, P.B.; de Bruijn, E.; Hao, W.; Macinnes, A.W.; Cuppen, E.; Simonis, M. Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes. Genome Biol. 2014, 15, R6. [Google Scholar] [CrossRef] [Green Version]
  20. Mackowiak, S.D.; Zauber, H.; Bielow, C.; Thiel, D.; Kutz, K.; Calviello, L.; Mastrobuoni, G.; Rajewsky, N.; Kempa, S.; Selbach, M.; et al. Extensive identification and analysis of conserved small ORFs in animals. Genome Biol. 2015, 16, 179. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  21. Yeasmin, F.; Yada, T.; Akimitsu, N. Micropeptides Encoded in Transcripts Previously Identified as Long Noncoding RNAs: A New Chapter in Transcriptomics and Proteomics. Front. Genet. 2018, 9, 144. [Google Scholar] [CrossRef] [PubMed]
  22. Clark, M.B.; Johnston, R.L.; Inostroza-Ponta, M.; Fox, A.H.; Fortini, E.; Moscato, P.; Dinger, M.E.; Mattick, J.S. Genome-wide analysis of long noncoding RNA stability. Genome Res. 2012, 22, 885–898. [Google Scholar] [CrossRef] [Green Version]
  23. Ponting, C.P.; Oliver, P.L.; Reik, W. Evolution and functions of long noncoding RNAs. Cell 2009, 136, 629–641. [Google Scholar] [CrossRef] [Green Version]
  24. Yao, R.W.; Wang, Y.; Chen, L.L. Cellular functions of long noncoding RNAs. Nat. Cell Biol. 2019, 21, 542–551. [Google Scholar] [CrossRef] [PubMed]
  25. López-Urrutia, E.; Bustamante Montes, L.P.; Ladrón de Guevara Cervantes, D.; Pérez-Plasencia, C.; Campos-Parra, A.D. Crosstalk Between Long Non-coding RNAs, Micro-RNAs and mRNAs: Deciphering Molecular Mechanisms of Master Regulators in Cancer. Front. Oncol. 2019, 9, 669. [Google Scholar] [CrossRef] [PubMed]
  26. Rashid, F.; Shah, A.; Shan, G. Long Non-coding RNAs in the Cytoplasm. Genom. Proteom. Bioinform. 2016, 14, 73–80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  27. Noh, J.H.; Kim, K.M.; McClusky, W.G.; Abdelmohsen, K.; Gorospe, M. Cytoplasmic functions of long noncoding RNAs. Wiley Interdiscip. Rev. RNA 2018, 9, e1471. [Google Scholar] [CrossRef]
  28. Goff, L.A.; Rinn, J.L. Linking RNA biology to lncRNAs. Genome Res. 2015, 25, 1456–1465. [Google Scholar] [CrossRef] [Green Version]
  29. Singh, D.K.; Prasanth, K.V. Functional insights into the role of nuclear-retained long noncoding RNAs in gene expression control in mammalian cells. Chromosome Res. 2013, 21, 695–711. [Google Scholar] [CrossRef] [Green Version]
  30. Lennox, K.A.; Behlke, M.A. Cellular localization of long non-coding RNAs affects silencing by RNAi more than by antisense oligonucleotides. Nucleic Acids Res. 2016, 44, 863–877. [Google Scholar] [CrossRef] [Green Version]
  31. Faghihi, M.A.; Zhang, M.; Huang, J.; Modarresi, F.; Van der Brug, M.P.; Nalls, M.A.; Cookson, M.R.; St-Laurent, G., 3rd; Wahlestedt, C. Evidence for natural antisense transcript-mediated inhibition of microRNA function. Genome Biol. 2010, 11, R56. [Google Scholar] [CrossRef] [Green Version]
  32. Zhang, J.; Liu, L.; Li, J.; Le, T.D. LncmiRSRN: Identification and analysis of long non-coding RNA related miRNA sponge regulatory network in human cancer. Bioinformatics 2018, 34, 4232–4240. [Google Scholar] [CrossRef]
  33. Zhang, Z.; Zhu, Z.; Watabe, K.; Zhang, X.; Bai, C.; Xu, M.; Wu, F.; Mo, Y.Y. Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ. 2013, 20, 1558–1568. [Google Scholar] [CrossRef] [Green Version]
  34. Li, W.; Zhai, L.; Wang, H.; Li, W.; Zhai, L.; Wang, H.; Liu, C.; Zhang, J.; Chen, W.; Wei, Q. Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer. Oncotarget 2016, 7, 27778–27786. [Google Scholar] [CrossRef] [Green Version]
  35. Xiao, J.; Lin, L.; Luo, D.; Shi, L.; Chen, W.; Fan, H.; Li, Z.; Ma, X.; Ni, P.; Yang, L.; et al. Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance. Oncogenesis 2020, 9, 29. [Google Scholar] [CrossRef]
  36. Mercer, T.R.; Neph, S.; Dinger, M.E.; Crawford, J.; Smith, M.A.; Shearwood, A.M.; Haugen, E.; Bracken, C.P.; Rackham, O.; Stamatoyannopoulos, J.A.; et al. The human mitochondrial transcriptome. Cell 2011, 146, 645–658. [Google Scholar] [CrossRef] [Green Version]
  37. Hu, G.; Lou, Z.; Gupta, M. The long non-coding RNA GAS5 cooperates with the eukaryotic translation initiation factor 4E to regulate c-Myc translation. PLoS ONE 2014, 9, e107016. [Google Scholar] [CrossRef] [Green Version]
  38. Cao, L.; Zhang, P.; Li, J.; Wu, M. LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1 mRNA stability in human cells. Elife 2017, 6, e30433. [Google Scholar] [CrossRef]
  39. Yang, F.; Zhang, H.; Mei, Y.; Wu, M. Reciprocal regulation of HIF-1α and lincRNA-p21 modulates the Warburg effect. Mol. Cell. 2014, 53, 88–100. [Google Scholar] [CrossRef] [Green Version]
  40. Zhu, P.; Wang, Y.; Huang, G.; Ye, B.; Liu, B.; Wu, J.; Du, Y.; He, L.; Fan, Z. lnc-β-Catm elicits EZH2-dependent β-catenin stabilization and sustains liver CSC self-renewal. Nat. Struct. Mol. Biol. 2016, 23, 631–639. [Google Scholar] [CrossRef]
  41. Bergmann, J.H.; Spector, D.L. Long non-coding RNAs: Modulators of nuclear structure and function. Curr. Opin. Cell Biol. 2014, 26, 10–18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Vance, K.W.; Ponting, C.P. Transcriptional regulatory functions of nuclear long noncoding RNAs. Trends Genet. 2014, 30, 348–355. [Google Scholar] [CrossRef] [Green Version]
  43. Quinodoz, S.; Guttman, M. Long noncoding RNAs: An emerging link between gene regulation and nuclear organization. Trends Cell Biol. 2014, 24, 651–663. [Google Scholar] [CrossRef] [Green Version]
  44. Chen, L.L. Linking Long Noncoding RNA Localization and Function. Trends Biochem. Sci. 2016, 41, 761–772. [Google Scholar] [CrossRef] [PubMed]
  45. Schmitt, A.M.; Chang, H.Y. Long Noncoding RNAs: At the Intersection of Cancer and Chromatin Biology. Cold Spring Harb. Perspect. Med. 2017, 7, a026492. [Google Scholar] [CrossRef] [Green Version]
  46. Jackson, R.J.; Hellen, C.U.; Pestova, T.V. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat. Rev. Mol. Cell Biol. 2010, 11, 113–127. [Google Scholar] [CrossRef] [Green Version]
  47. Dever, T.E. Gene-specific regulation by general translation factors. Cell 2002, 108, 545–556. [Google Scholar] [CrossRef] [Green Version]
  48. Ali, M.U.; Ur Rahman, M.S.; Jia, Z.; Jiang, C. Eukaryotic translation initiation factors and cancer. Tumor Biol. 2017, 39, 1010428317709805. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  49. Grifo, J.A.; Tahara, S.M.; Morgan, M.A.; Shatkin, A.J.; Merrick, W.C. New initiation factor activity required for globin mRNA translation. J. Biol. Chem. 1983, 258, 5804–5810. [Google Scholar] [CrossRef]
  50. Hinnebusch, A.G. Molecular mechanism of scanning and start codon selection in eukaryotes. Microbiol. Mol. Biol. Rev. 2011, 75, 434–467. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  51. Llácer, J.L.; Hussain, T.; Saini, A.K.; Nanda, J.S.; Kaur, S.; Gordiyenko, Y.; Kumar, R.; Hinnebusch, A.G.; Lorsch, J.R.; Ramakrishnan, V. Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition. eLife 2018, 7, e39273. [Google Scholar] [CrossRef]
  52. Voorhees, R.M.; Ramakrishnan, V. Structural basis of the translational elongation cycle. Annu. Rev. Biochem. 2013, 82, 203–236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Rodnina, M.V.; Gromadski, K.B.; Kothe, U.; Wieden, H.J. Recognition and selection of tRNA in translation. FEBS Lett. 2005, 579, 938–942. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  54. Stansfield, I.; Jones, K.M.; Kushnirov, V.V.; Dagkesamanskaya, A.R.; Poznyakovski, A.I.; Paushkin, S.V.; Nierras, C.R.; Cox, B.S.; Ter-Avanesyan, M.D.; Tuite, M.F. The products of the SUP45 (eRF1) and SUP35 genes interact to mediate translation termination in Saccharomyces cerevisiae. EMBO J. 1995, 14, 4365–4373. [Google Scholar] [CrossRef]
  55. Zhouravleva, G.; Frolova, L.; Le Goff, X.; Le Guellec, R.; Inge-Vechtomov, S.; Kisselev, L.; Philippe, M. Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRF1 and eRF3. EMBO J. 1995, 14, 4065–4072. [Google Scholar] [CrossRef]
  56. Alkalaeva, E.Z.; Pisarev, A.V.; Frolova, L.Y.; Kisselev, L.L.; Pestova, T.V. In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell 2006, 125, 1125–1136. [Google Scholar] [CrossRef] [Green Version]
  57. Salas-Marco, J.; Bedwell, D.M. GTP hydrolysis by eRF3 facilitates stop codon decoding during eukaryotic translation termination. Mol. Cell Biol. 2004, 24, 7769–7778. [Google Scholar] [CrossRef] [Green Version]
  58. Frolova, L.; Le Goff, X.; Zhouravleva, G.; Davydova, E.; Philippe, M.; Kisselev, L. Eukaryotic polypeptide chain release factor eRF3 is an eRF1- and ribosome-dependent guanosine triphosphatase. RNA 1996, 2, 334–341. [Google Scholar]
  59. Jia, X.; Shi, L.; Wang, X.; Luo, L.; Ling, L.; Yin, J.; Song, Y.; Zhang, Z.; Qiu, N.; Liu, H.; et al. KLF5 regulated lncRNA RP1 promotes the growth and metastasis of breast cancer via repressing p27kip1 translation. Cell Death Dis. 2019, 10, 373. [Google Scholar] [CrossRef] [Green Version]
  60. Hu, G.; Witzig, T.E.; Gupta, M. Novel Long Non-Coding RNA, SNHG4 Complex With Eukaryotic Initiation Factor-4E and Regulate Aberrant Protein Translation In Mantle Cell Lymphoma: Implications For Novel Biomarker. Blood 2013, 122, 81. [Google Scholar] [CrossRef]
  61. Gumireddy, K.; Li, A.; Yan, J.; Setoyama, T.; Johannes, G.J.; Orom, U.A.; Tchou, J.; Liu, Q.; Zhang, L.; Speicher, D.W.; et al. Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step. EMBO J. 2013, 32, 2672–2684. [Google Scholar] [CrossRef]
  62. Wang, H.; Iacoangeli, A.; Popp, S.; Muslimov, I.A.; Imataka, H.; Sonenberg, N.; Lomakin, I.B.; Tiedge, H. Dendritic BC1 RNA: Functional role in regulation of translation initiation. J. Neurosci. 2002, 22, 10232–10241. [Google Scholar] [CrossRef] [Green Version]
  63. Wang, H.; Iacoangeli, A.; Lin, D.; Williams, K.; Denman, R.B.; Hellen, C.U.; Tiedge, H. Dendritic BC1 RNA in translational control mechanisms. J. Cell Biol. 2005, 171, 811–821. [Google Scholar] [CrossRef] [Green Version]
  64. Gu, H.; Chen, J.; Song, Y.; Shao, H. Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway. Cell Physiol. Biochem. 2018, 51, 2136–2147. [Google Scholar] [CrossRef] [PubMed]
  65. Gao, Y.F.; Liu, J.Y.; Mao, X.Y.; He, Z.W.; Zhu, T.; Wang, Z.B.; Li, X.; Yin, J.Y.; Zhang, W.; Zhou, H.H.; et al. LncRNA FOXD1-AS1 acts as a potential oncogenic biomarker in glioma. CNS Neurosci. Ther. 2020, 26, 66–75. [Google Scholar] [CrossRef]
  66. Park, S.A.; Kim, L.K.; Kim, Y.T.; Heo, T.H.; Kim, H.J. Long non-coding RNA steroid receptor activator promotes the progression of endometrial cancer via Wnt/β-catenin signaling pathway. Int. J. Biol. Sci. 2020, 16, 99–115. [Google Scholar] [CrossRef] [Green Version]
  67. Guo, C.; Gong, M.; Li, Z. Knockdown of lncRNA MCM3AP-AS1 Attenuates Chemoresistance of Burkitt Lymphoma to Doxorubicin Treatment via Targeting the miR-15a/EIF4E Axis. Cancer Manag. Res. 2020, 12, 5845–5855. [Google Scholar] [CrossRef] [PubMed]
  68. Liu, W.; Che, J.; Gu, Y.; Song, L. LncRNA SNHG12 promotes proliferation and migration of vascular smooth muscle cells via targeting miR-766-5p/EIF5A. Res. Square 2020. [Google Scholar] [CrossRef]
  69. Wu, S.; Zhang, L.; Deng, J.; Guo, B.; Li, F.; Wang, Y.; Wu, R.; Zhang, S.; Lu, J.; Zhou, Y. A Novel Micropeptide Encoded by Y-Linked LINC00278 Links Cigarette Smoking and AR Signaling in Male Esophageal Squamous Cell Carcinoma. Cancer Res. 2020, 80, 2790–2803. [Google Scholar] [CrossRef] [Green Version]
  70. Janku, F.; Yap, T.A.; Meric-Bernstam, F. Targeting the PI3K pathway in cancer: Are we making headway? Nat. Rev. Clin. Oncol. 2018, 15, 273–291. [Google Scholar] [CrossRef]
  71. Kim, E.K.; Choi, E.J. Pathological roles of MAPK signaling pathways in human diseases. Biochim. Biophys. Acta 2010, 1802, 396–405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  72. Fruman, D.A.; Chiu, H.; Hopkins, B.D.; Bagrodia, S.; Cantley, L.C.; Abraham, R.T. The PI3K Pathway in Human Disease. Cell 2017, 170, 605–635. [Google Scholar] [CrossRef] [Green Version]
  73. Braicu, C.; Buse, M.; Busuioc, C.; Drula, R.; Gulei, D.; Raduly, L.; Rusu, A.; Irimie, A.; Atanasov, A.G.; Slaby, O.; et al. A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers 2019, 11, 1618. [Google Scholar] [CrossRef] [Green Version]
  74. Xu, F.; Na, L.; Li, Y.; Chen, L. Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours. Cell Biosci. 2020, 10, 54. [Google Scholar] [CrossRef] [Green Version]
  75. Morrison, D.K. MAP kinase pathways. Cold Spring Harb. Perspect. Biol. 2012, 4, a011254. [Google Scholar] [CrossRef]
  76. Dhillon, A.S.; Hagan, S.; Rath, O.; Kolch, W. MAP kinase signalling pathways in cancer. Oncogene 2007, 26, 3279–3290. [Google Scholar] [CrossRef] [Green Version]
  77. Heesom, K.J.; Denton, R.M. Dissociation of the eukaryotic initiation factor-4E/4E-BP1 complex involves phosphorylation of 4E-BP1 by an mTOR-associated kinase. FEBS Lett. 1999, 457, 489–493. [Google Scholar] [CrossRef] [Green Version]
  78. Holz, M.K.; Ballif, B.A.; Gygi, S.P.; Blenis, J. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell 2005, 123, 569–580. [Google Scholar] [CrossRef] [Green Version]
  79. Browne, G.J.; Proud, C.G. A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin. Mol. Cell. Biol. 2004, 24, 2986–2997. [Google Scholar] [CrossRef] [Green Version]
  80. Knebel, A.; Morrice, N.; Cohen, P. A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. EMBO J. 2001, 20, 4360–4369. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  81. Knebel, A.; Haydon, C.E.; Morrice, N.; Cohen, P. Stress-induced regulation of eEF2 kinase by SB203580-sensitive and -insensitive pathways. Biochem. J. 2002, 367, 525–532. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  82. Cao, Z.; Wu, P.; Su, M.; Ling, H.; Khoshaba, R.; Huang, C.; Gao, H.; Zhao, Y.; Chen, J.; Liao, Q.; et al. Long non-coding RNA UASR1 promotes proliferation and migration of breast cancer cells through the AKT/mTOR pathway. J. Cancer 2019, 10, 2025–2034. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  83. Zhong, M.E.; Chen, Y.; Zhang, G.; Xu, L.; Ge, W.; Wu, B. LncRNA H19 regulates PI3K-Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: Integrative analysis of dysregulated ncRNA-associated ceRNA network. Cancer Cell Int. 2019, 19, 148. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Wu, Z.R.; Yan, L.; Liu, Y.T.; Cao, L.; Guo, Y.H.; Zhang, Y.; Yao, H.; Cai, L.; Shang, H.B.; Rui, W.W.; et al. Inhibition of mTORC1 by lncRNA H19 via disrupting 4E-BP1/Raptor interaction in pituitary tumours. Nat. Commun. 2018, 9, 4624. [Google Scholar] [CrossRef] [Green Version]
  85. Yang, Y.; Chen, D.; Liu, H.; Yang, K. Increased expression of lncRNA CASC9 promotes tumor progression by suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway in oral squamous cell carcinoma. Cell Death Dis. 2019, 10, 41. [Google Scholar] [CrossRef] [Green Version]
  86. Gao, X.; Wang, N.; Wu, S.; Cui, H.; An, X.; Yang, Y. Long non-coding RNA FER1L4 inhibits cell proliferation and metastasis through regulation of the PI3K/AKT signaling pathway in lung cancer cells. Mol. Med. Rep. 2019, 20, 182–190. [Google Scholar] [CrossRef] [Green Version]
  87. Malakar, P.; Stein, I.; Saragovi, A.; Winkler, R.; Stern-Ginossar, N.; Berger, M.; Pikarsky, E.; Karni, R. Long Noncoding RNA MALAT1 Regulates Cancer Glucose Metabolism by Enhancing mTOR-Mediated Translation of TCF7L2. Cancer Res. 2019, 79, 2480–2493. [Google Scholar] [CrossRef] [Green Version]
  88. Jiang, W.; Kai, J.; Li, D.; Wei, Z.; Wang, Y.; Wang, W. lncRNA HOXB-AS3 exacerbates proliferation, migration, and invasion of lung cancer via activating the PI3K-AKT pathway. J. Cell Physiol. 2020, 235, 7194–7203. [Google Scholar] [CrossRef]
  89. Huang, Y.; Zhang, J.; Hou, L.; Wang, G.; Liu, H.; Zhang, R.; Chen, X.; Zhu, J. LncRNA AK023391 promotes tumorigenesis and invasion of gastric cancer through activation of the PI3K/Akt signaling pathway. J. Exp. Clin. Cancer Res. 2017, 36, 194. [Google Scholar] [CrossRef]
  90. Li, C.; Liang, G.; Yang, S.; Sui, J.; Wu, W.; Xu, S.; Ye, Y.; Shen, B.; Zhang, X.; Zhang, Y. LncRNA-LOC101928316 contributes to gastric cancer progression through regulating PI3K-Akt-mTOR signaling pathway. Cancer Med. 2019, 8, 4428–4440. [Google Scholar] [CrossRef] [Green Version]
  91. Yuan, Z.; Li, Z. Long noncoding RNA UCA1 facilitates cell proliferation and inhibits apoptosis in retinoblastoma by activating the PI3K/Akt pathway. Transl. Cancer Res. 2020, 9. [Google Scholar] [CrossRef]
  92. Zou, Y.; Zhang, B.; Mao, Y.; Zhang, H.; Hong, W. Long non-coding RNA OECC promotes cell proliferation and metastasis through the PI3K/Akt/mTOR signaling pathway in human lung cancer. Oncol. Lett. 2019, 18, 3017–3024. [Google Scholar] [CrossRef] [Green Version]
  93. Liu, J.; Chen, M.; Ma, L.; Dang, X.; Du, G. LncRNA GAS5 Suppresses the Proliferation and Invasion of Osteosarcoma Cells via the miR-23a-3p/PTEN/PI3K/AKT Pathway. Cell Transplant. 2020, 29, 963689720953093. [Google Scholar] [CrossRef]
  94. Wang, M.R.; Fang, D.; Di, M.P.; Guan, J.L.; Wang, G.; Liu, L.; Sheng, J.Q.; Tian, D.A.; Li, P.Y. Long non-coding RNA LINC01503 promotes the progression of hepatocellular carcinoma via activating MAPK/ERK pathway. Int. J. Med. Sci. 2020, 17, 1224–1234. [Google Scholar] [CrossRef]
  95. Fang, K.; Hu, C.; Zhang, X.; Hou, Y.; Gao, D.; Guo, Z.; Li, L. LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK signalling pathway. Carcinogenesis 2020, 41, 1273–1281. [Google Scholar] [CrossRef] [PubMed]
  96. Qian, G.; Jin, X.; Zhang, L. LncRNA FENDRR Upregulation Promotes Hepatic Carcinoma Cells Apoptosis by Targeting miR-362-5p Via NPR3 and p38-MAPK Pathway. Cancer Biother. Radiopharm. 2020, 35, 629–639. [Google Scholar] [CrossRef]
  97. Zhang, T.; Hu, H.; Yan, G.; Wu, T.; Liu, S.; Chen, W.; Ning, Y.; Lu, Z. Long Non-Coding RNA and Breast Cancer. Technol. Cancer Res. Treat. 2019, 18, 1533033819843889. [Google Scholar] [CrossRef] [Green Version]
  98. Zhou, W.; Chen, L.; Li, C.; Huang, R.; Guo, M.; Ning, S.; Ji, J.; Guo, X.; Lou, G.; Jia, X.; et al. The multifaceted roles of long noncoding RNAs in pancreatic cancer: An update on what we know. Cancer Cell Int. 2020, 20, 41. [Google Scholar] [CrossRef] [Green Version]
  99. Huang, Z.; Zhou, J.K.; Peng, Y.; He, W.; Huang, C. The role of long noncoding RNAs in hepatocellular carcinoma. Mol. Cancer 2020, 19, 77. [Google Scholar] [CrossRef] [Green Version]
  100. Siddiqui, H.; Al-Ghafari, A.; Choudhry, H.; Al Doghaither, H. Roles of long non-coding RNAs in colorectal cancer tumorigenesis: A Review. Mol. Clin. Oncol. 2019, 11, 167–172. [Google Scholar] [CrossRef]
  101. Gao, J.; Wang, F.; Wu, P.; Chen, Y.; Jia, Y. Aberrant LncRNA Expression in Leukemia. J. Cancer 2020, 11, 4284–4296. [Google Scholar] [CrossRef] [PubMed]
  102. Cheng, D.; Fan, J.; Ma, Y.; Zhou, Y.; Qin, K.; Shi, M.; Yang, J. LncRNA SNHG7 promotes pancreatic cancer proliferation through ID4 by sponging miR-342-3p. Cell Biosci. 2019, 9, 28. [Google Scholar] [CrossRef] [Green Version]
  103. Wei, W.; Liu, Y.; Lu, Y.; Yang, B.; Tang, L. LncRNA XIST Promotes Pancreatic Cancer Proliferation Through miR-133a/EGFR. J. Cell Biochem. 2017, 118, 3349–3358. [Google Scholar] [CrossRef] [PubMed]
  104. Berteaux, N.; Lottin, S.; Monté, D.; Pinte, S.; Quatannens, B.; Coll, J.; Hondermarck, H.; Curgy, J.J.; Dugimont, T.; Adriaenssens, E. H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J. Biol. Chem. 2005, 280, 29625–29636. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  105. Tang, J.; Li, Y.; Sang, Y.; Yu, B.; Lv, D.; Zhang, W.; Feng, H. LncRNA PVT1 regulates triple-negative breast cancer through KLF5/beta-catenin signaling. Oncogene 2018, 37, 4723–4734. [Google Scholar] [CrossRef]
  106. Zhong, H.; Yang, J.; Zhang, B.; Wang, X.; Pei, L.; Zhang, L.; Lin, Z.; Wang, Y.; Wang, C. LncRNA GACAT3 predicts poor prognosis and promotes cell proliferation in breast cancer through regulation of miR-497/CCND2. Cancer Biomark. 2018, 22, 787–797. [Google Scholar] [CrossRef] [PubMed]
  107. Zhang, M.; Wu, W.B.; Wang, Z.W.; Wang, X.H. lncRNA NEAT1 is closely related with progression of breast cancer via promoting proliferation and EMT. Eur. Rev. Med. Pharmacol. Sci. 2017, 21, 1020–1026. [Google Scholar]
  108. You, Z.; Liu, C.; Wang, C.; Ling, Z.; Wang, Y.; Wang, Y.; Zhang, M.; Chen, S.; Xu, B.; Guan, H.; et al. LncRNA CCAT1 Promotes Prostate Cancer Cell Proliferation by Interacting with DDX5 and MIR-28-5P. Mol. Cancer Ther. 2019, 18, 2469–2479. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  109. Yang, B.; Gao, G.; Wang, Z.; Sun, D.; Wei, X.; Ma, Y.; Ding, Y. Long non-coding RNA HOTTIP promotes prostate cancer cells proliferation and migration by sponging miR-216a-5p. Biosci. Rep. 2018, 38, BSR20180566. [Google Scholar] [CrossRef] [Green Version]
  110. Zhang, Y.; Su, X.; Kong, Z.; Fu, F.; Zhang, P.; Wang, D.; Wu, H.; Wan, X.; Li, Y. An androgen reduced transcript of LncRNA GAS5 promoted prostate cancer proliferation. PLoS ONE 2017, 12, e0182305. [Google Scholar] [CrossRef] [Green Version]
  111. Park, S.M.; Choi, E.Y.; Bae, D.H.; Sohn, H.A.; Kim, S.Y.; Kim, Y.J. The LncRNA EPEL Promotes Lung Cancer Cell Proliferation Through E2F Target Activation. Cell Physiol. Biochem. 2018, 45, 1270–1283. [Google Scholar] [CrossRef] [PubMed]
  112. Nie, F.Q.; Sun, M.; Yang, J.S.; Xie, M.; Xu, T.P.; Xia, R.; Liu, Y.W.; Liu, X.H.; Zhang, E.B.; Lu, K.H.; et al. Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol. Cancer Ther. 2015, 14, 268–277. [Google Scholar] [CrossRef] [Green Version]
  113. Feng, C.; Zhao, Y.; Li, Y.; Zhang, T.; Ma, Y.; Liu, Y. LncRNA MALAT1 Promotes Lung Cancer Proliferation and Gefitinib Resistance by Acting as a miR-200a Sponge. Arch. Bronconeumol. 2019, 55, 627–633. [Google Scholar] [CrossRef] [PubMed]
  114. Wu, R.; Li, L.; Bai, Y.; Yu, B.; Xie, C.; Wu, H.; Zhang, Y.; Huang, L.; Yan, Y.; Li, X.; et al. The long noncoding RNA LUCAT1 promotes colorectal cancer cell proliferation by antagonizing Nucleolin to regulate MYC expression. Cell Death Dis. 2020, 11, 908. [Google Scholar] [CrossRef] [PubMed]
  115. Wang, Y.; Lu, Z.; Wang, N.; Feng, J.; Zhang, J.; Luan, L.; Zhao, W.; Zeng, X. Long noncoding RNA DANCR promotes colorectal cancer proliferation and metastasis via miR-577 sponging. Exp. Mol. Med. 2018, 50, 1–17. [Google Scholar] [CrossRef] [Green Version]
  116. Liu, Z.; Sun, M.; Lu, K.; Liu, J.; Zhang, M.; Wu, W.; De, W.; Wang, Z.; Wang, R. The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS ONE 2013, 8, e77293. [Google Scholar]
  117. Pan, Y.; Chen, J.; Tao, L.; Zhang, K.; Wang, R.; Chu, X.; Chen, L. Long noncoding RNA ROR regulates chemoresistance in docetaxel-resistant lung adenocarcinoma cells via epithelial mesenchymal transition pathway. Oncotarget 2017, 8, 33144–33158. [Google Scholar] [CrossRef] [Green Version]
  118. Wang, Y.; Zhang, D.; Wu, K.; Zhao, Q.; Nie, Y.; Fan, D. Long noncoding RNA MRUL promotes ABCB1 expression in multidrug-resistant gastric cancer cell sublines. Mol. Cell Biol. 2014, 34, 3182–3193. [Google Scholar] [CrossRef] [Green Version]
  119. Chen, J.; Zhang, K.; Song, H.; Wang, R.; Chu, X.; Chen, L. Long noncoding RNA CCAT1 acts as an oncogene and promotes chemoresistance in docetaxel-resistant lung adenocarcinoma cells. Oncotarget 2016, 7, 62474–62489. [Google Scholar] [CrossRef] [Green Version]
  120. Jiang, Y.Z.; Liu, Y.R.; Xu, X.E.; Jin, X.; Hu, X.; Yu, K.D.; Shao, Z.M. Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value. Cancer Res. 2016, 76, 2105–2114. [Google Scholar] [CrossRef] [Green Version]
  121. Ren, J.; Ding, L.; Zhang, D.; Shi, G.; Xu, Q.; Shen, S.; Wang, Y.; Wang, T.; Hou, Y. Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19. Theranostics 2018, 8, 3932–3948. [Google Scholar] [CrossRef] [PubMed]
  122. Fang, Z.; Chen, W.; Yuan, Z.; Liu, X.; Jiang, H. LncRNA-MALAT1 contributes to the cisplatin-resistance of lung cancer by upregulating MRP1 and MDR1 via STAT3 activation. Biomed. Pharmacother. 2018, 101, 536–542. [Google Scholar] [CrossRef]
  123. Lan, W.G.; Xu, D.H.; Xu, C.; Ding, C.L.; Ning, F.L.; Zhou, Y.L.; Ma, L.B.; Liu, C.M.; Han, X. Silencing of long non-coding RNA ANRIL inhibits the development of multidrug resistance in gastric cancer cells. Oncol. Rep. 2016, 36, 263–270. [Google Scholar] [CrossRef] [Green Version]
  124. Zhu, J.; Zhang, R.; Yang, D.; Li, J.; Yan, X.; Jin, K.; Li, W.; Liu, X.; Zhao, J.; Shang, W.; et al. Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1. Cell Physiol. Biochem. 2018, 51, 113–128. [Google Scholar] [CrossRef]
  125. Liu, Y.; Wang, J.; Dong, L.; Xia, L.; Zhu, H.; Li, Z.; Yu, X. Long Noncoding RNA HCP5 Regulates Pancreatic Cancer Gemcitabine (GEM) Resistance By Sponging Hsa-miR-214-3p To Target HDGF. Oncol. Ther. 2019, 12, 8207–8216. [Google Scholar] [CrossRef] [Green Version]
  126. Zhang, X.; Zhao, P.; Wang, C.; Xin, B. SNHG14 enhances gemcitabine resistance by sponging miR-101 to stimulate cell autophagy in pancreatic cancer. Biochem. Biophys. Res. Commun. 2019, 510, 508–514. [Google Scholar] [CrossRef]
  127. Chang, K.C.; Diermeier, S.D.; Yu, A.T.; Brine, L.D.; Russo, S.; Bhatia, S.; Alsudani, H.; Kostroff, K.; Bhuiya, T.; Brogi, E.; et al. MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression. Nat. Commun. 2020, 11, 6438. [Google Scholar] [CrossRef]
  128. Zhang, Y.; Huang, W.; Yuan, Y.; Li, J.; Wu, J.; Yu, J.; He, Y.; Wei, Z.; Zhang, C. Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1. J. Exp. Clin. Cancer Res. 2020, 39, 141. [Google Scholar] [CrossRef]
  129. Xing, Z.; Lin, A.; Li, C.; Liang, K.; Wang, S.; Liu, Y.; Park, P.K.; Qin, L.; Wei, Y.; Hawke, D.H.; et al. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell 2014, 159, 1110–1125. [Google Scholar] [CrossRef] [Green Version]
  130. Leng, X.; Ding, X.; Wang, S.; Fang, T.; Shen, W.; Xia, W.; You, R.; Xu, K.; Yin, R. Long noncoding RNA AFAP1-AS1 is upregulated in NSCLC and associated with lymph node metastasis and poor prognosis. Oncol. Lett. 2018, 16, 727–732. [Google Scholar] [CrossRef] [Green Version]
  131. Deng, S.J.; Chen, H.Y.; Ye, Z.; Deng, S.C.; Zhu, S.; Zeng, Z.; He, C.; Liu, M.L.; Huang, K.; Zhong, J.X.; et al. Hypoxia-induced LncRNA-BX111 promotes metastasis and progression of pancreatic cancer through regulating ZEB1 transcription. Oncogene 2018, 37, 5811–5828. [Google Scholar] [CrossRef] [PubMed]
  132. Luo, Y.; Wang, Q.; Teng, L.; Zhang, J.; Song, J.; Bo, W.; Liu, D.; He, Y.; Tan, A. LncRNA DANCR promotes proliferation and metastasis in pancreatic cancer by regulating miRNA-33b. FEBS Open Bio 2020, 10, 18–27. [Google Scholar] [CrossRef] [PubMed]
  133. Zhang, M.; Zhao, Y.; Zhang, Y.; Wang, D.; Gu, S.; Feng, W.; Peng, W.; Gong, A.; Xu, M. LncRNA UCA1 promotes migration and invasion in pancreatic cancer cells via the Hippo pathway. Biochim. Biophys. Acta Mol. Basis Dis. 2018, 1864, 1770–1782. [Google Scholar] [CrossRef]
  134. Sun, F.; Wu, K.; Yao, Z.; Mu, X.; Zheng, Z.; Sun, M.; Wang, Y.; Liu, Z.; Zhu, Y. Long Noncoding RNA PVT1 Promotes Prostate Cancer Metastasis by Increasing NOP2 Expression via Targeting Tumor Suppressor MicroRNAs. OncoTargets Ther. 2020, 13, 6755–6765. [Google Scholar] [CrossRef]
  135. Yang, M.H.; Hu, Z.Y.; Xu, C.; Xie, L.Y.; Wang, X.Y.; Chen, S.Y.; Li, Z.G. MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9. Biochim. Biophys. Acta 2015, 1852, 166–174. [Google Scholar] [CrossRef] [Green Version]
  136. Gupta, R.A.; Shah, N.; Wang, K.C.; Kim, J.; Horlings, H.M.; Wong, D.J.; Tsai, M.C.; Hung, T.; Argani, P.; Rinn, J.L.; et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010, 464, 1071–1076. [Google Scholar] [CrossRef] [PubMed]
  137. Ling, H.; Spizzo, R.; Atlasi, Y.; Nicoloso, M.; Shimizu, M.; Redis, R.S.; Nishida, N.; Gafà, R.; Song, J.; Guo, Z.; et al. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res. 2013, 23, 1446–1461. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  138. Tee, A.E.; Liu, B.; Song, R.; Li, J.; Pasquier, E.; Cheung, B.B.; Jiang, C.; Marshall, G.M.; Haber, M.; Norris, M.D.; et al. The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression. Oncotarget 2016, 7, 8663–8675. [Google Scholar] [CrossRef]
  139. Fu, W.M.; Lu, Y.F.; Hu, B.G.; Liang, W.C.; Zhu, X.; Yang, H.D.; Li, G.; Zhang, J.F. Long noncoding RNA Hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways. Oncotarget 2016, 7, 4712–4723. [Google Scholar] [CrossRef] [Green Version]
  140. Yuan, S.X.; Yang, F.; Yang, Y.; Tao, Q.F.; Zhang, J.; Huang, G.; Yang, Y.; Wang, R.Y.; Yang, S.; Huo, X.S.; et al. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology 2012, 56, 2231–2241. [Google Scholar] [CrossRef]
  141. Zhang, J.X.; Chen, Z.H.; Chen, D.L.; Tian, X.P.; Wang, C.Y.; Zhou, Z.W.; Gao, Y.; Xu, Y.; Chen, C.; Zheng, Z.S.; et al. LINC01410-miR-532-NCF2-NF-kB feedback loop promotes gastric cancer angiogenesis and metastasis. Oncogene 2018, 37, 2660–2675. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  142. Cai, H.; Liu, X.; Zheng, J.; Xue, Y.; Ma, J.; Li, Z.; Xi, Z.; Li, Z.; Bao, M.; Liu, Y. Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma. Oncogene 2017, 36, 318–331. [Google Scholar] [CrossRef] [PubMed]
  143. Zhao, J.; Du, P.; Cui, P.; Qin, Y.; Hu, C.; Wu, J.; Zhou, Z.; Zhang, W.; Qin, L.; Huang, G. LncRNA PVT1 promotes angiogenesis via activating the STAT3/VEGFA axis in gastric cancer. Oncogene 2018, 37, 4094–4109. [Google Scholar] [CrossRef]
  144. Lin, X.; Yang, F.; Qi, X.; Li, Q.; Wang, D.; Yi, T.; Yin, R.; Zhao, X.; Zhong, X.; Bian, C. LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR-145. Mol. Carcinog. 2019, 58, 2286–2296. [Google Scholar] [CrossRef]
  145. Guo, Z.; Wang, X.; Yang, Y.; Chen, W.; Zhang, K.; Teng, B.; Huang, C.; Zhao, Q.; Qiu, Z. Hypoxic Tumor-Derived Exosomal Long Noncoding RNA UCA1 Promotes Angiogenesis via miR-96-5p/AMOTL2 in Pancreatic Cancer. Mol. Ther. Nucl. Acids 2020, 22, 179–195. [Google Scholar] [CrossRef]
  146. Jiang, X.; Yan, Y.; Hu, M.; Chen, X.; Wang, Y.; Dai, Y.; Wu, D.; Wang, Y.; Zhuang, Z.; Xia, H. Increased level of H19 long noncoding RNA promotes invasion, angiogenesis, and stemness of glioblastoma cells. J. Neurosurg. 2016, 124, 129–136. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  147. Zhang, C.; Luo, Y.; Cao, J.; Wang, X.; Miao, Z.; Shao, G. Exosomal lncRNA FAM225A accelerates esophageal squamous cell carcinoma progression and angiogenesis via sponging miR-206 to upregulate NETO2 and FOXP1 expression. Cancer Med. 2020, 9, 8600–8611. [Google Scholar] [CrossRef] [PubMed]
  148. Zhang, X.; Sun, Z.; Zou, Y. LncRNA NEAT1 exacerbates non-small cell lung cancer by upregulating EIF4G2 via miR-582-5p sponging. Arch. Biol. Sci. 2020, 72, 243–252. [Google Scholar] [CrossRef] [Green Version]
  149. Fang, Q.L.; Zhou, J.Y.; Xiong, Y.; Xiong, Y.; Xie, C.R.; Wang, F.Q.; Li, Y.T.; Yin, Z.Y.; Luo, G.H. Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis. Biosci. Rep. 2020, 40, BSR20200297. [Google Scholar] [CrossRef] [Green Version]
  150. Hu, M.; Yang, J. Down-regulation of lncRNA UCA1 enhances radiosensitivity in prostate cancer by suppressing EIF4G1 expression via sponging miR-331-3p. Cancer Cell Int. 2020, 20, 449. [Google Scholar] [CrossRef]
  151. Hansji, H.; Leung, E.Y.; Baguley, B.C.; Finlay, G.J.; Cameron-Smith, D.; Figueiredo, V.C.; Askarian-Amiri, M.E. ZFAS1: A long noncoding RNA associated with ribosomes in breast cancer cells. Biol. Direct. 2016, 11, 62. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  152. Liu, P.Y.; Tee, A.E.; Milazzo, G.; Hannan, K.M.; Maag, J.; Mondal, S.; Atmadibrata, B.; Bartonicek, N.; Peng, H.; Ho, N.; et al. The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35. Nat. Commun. 2019, 10, 5026. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  153. Song, J.; Ahn, C.; Chun, C.H.; Jin, E.J. A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J. Orthop. Res. 2014, 32, 1628–1635. [Google Scholar] [CrossRef] [PubMed]
Ncrna 07 00016 g001 550
Figure 1. Some lncRNAs are identified to be involved in aggressive characteristics of some common types of cancers [61,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147].
Figure 1. Some lncRNAs are identified to be involved in aggressive characteristics of some common types of cancers [61,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147].
Ncrna 07 00016 g001
Ncrna 07 00016 g002 550
Figure 2. The mechanisms of action of lncRNAs on the regulation of cancer-related protein translation [31,34,35,38,64,67,68,82,84,85,86,87,148,151,153].
Figure 2. The mechanisms of action of lncRNAs on the regulation of cancer-related protein translation [31,34,35,38,64,67,68,82,84,85,86,87,148,151,153].
Ncrna 07 00016 g002
Table
Table 1. The list of long non-coding RNAs (lncRNAs) involved in regulation of translational factors [37,59,60,61,62,63,64,65,66,67,68,69].
Table 1. The list of long non-coding RNAs (lncRNAs) involved in regulation of translational factors [37,59,60,61,62,63,64,65,66,67,68,69].
LncRNATranslation FactorFunctionReference
GAS5Binds to eIF4E and prevents formation of initiation complex (eIF4F)Decreases translation of c-Myc[37]
RP1-5O6.5Interacts with eIF4E and prevents binding to eIF4GPromotes breast cancer metastasis by inhibiting translation of p27Kip1[59]
SNHG1 and SNGH4 Bind to eIF4E and dysregulate itEnhance translation and contribute aggressiveness of lymphoma cells[60]
treRNAPromotes the formation of a treRNA-associated protein (treRNP) complex and suppresses translation by binding to eEIF4G1 treRNP complex reduces translation efficiency of E-cadherin and decreases tumor metastasis [61]
BC1Interacts with eIF4A and poly(A)-binding protein (PABP)Represses translation[62,63]
GAPLINCPositively regulates eEF2K expression by sponging miR-661Promotes tumorigenesis of non-small cell lung cancer cells[64]
SRABinds and increases the expression of eIF4E-binding protein 1 (eIF4E-BP1)Increases the activity of Wnt/ β-catenin signaling and promotes aggressive characteristics of endometrial cancer[66]
MCM3AP-AS1Positively regulates the expression of eIF4E by using miR15a as a spongePromotes translation and contributes doxorubicin resistance[67]
SNGH12Binds to miR-766-5p, which is a negative regulator of eIF5ATargets miR-766-5p/eIF5A axis and enhances invasion of vascular smooth muscle cells [68]
LNC00278Decreases eEF2K expressionMicropeptide of lncRNA, YY1BM, represses the eEF2K/eEF2 axis[69]
Table
Table 2. lncRNAs in the regulation of signaling pathways and their roles in various cancers [87,88,89,90,91,92,93,94,95,96].
Table 2. lncRNAs in the regulation of signaling pathways and their roles in various cancers [87,88,89,90,91,92,93,94,95,96].
LncRNATargetFunctionReference
MALAT1mTOR signalingImproves glucose metabolism to contribute aggressiveness in hepatocellular carcinoma cells[87]
HOXB-AS3PI3K/AKT signalingIncreases proliferation, migration, and invasion of lung cancer cells[88]
AK023391PI3K/AKT signaling Promotes tumorigenesis and invasion of gastric cancer [89]
LOC101928316PI3K/AKT/mTOR signalingInhibits cell proliferation, invasion and tumorigenesis of gastric cancer cells[90]
UCA1PI3K/AKT signalingPromotes cell proliferation and inhibits apoptosis in retinoblastoma cells [91]
OECCPI3K/AKT/mTOR signalingIncreases proliferation, migration and invasion of lung cancer cells[92]
GAS5PTEN/PI3K/AKT signalingSuppresses proliferation and invasion of osteosarcoma cells and promotes PTEN expression by sponging miR-23a-3p[93]
LINC01503MAPK/ERK signalingIncreases proliferation and tumor forming-ability of hepatocellular carcinoma cells[94]
ST8SIA6-AS1p38 MAPK signalingPromotes proliferation, migration and invasion of breast cancer cells[95]
FENDRRp38 MAPK signalingInhibits cell proliferation and induces apoptosis in hepatocellular carcinoma cells [96]
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Karakas, D.; Ozpolat, B. The Role of LncRNAs in Translation. Non-Coding RNA 2021, 7, 16. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010016

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Karakas D, Ozpolat B. The Role of LncRNAs in Translation. Non-Coding RNA. 2021; 7(1):16. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010016

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Karakas, Didem, and Bulent Ozpolat. 2021. "The Role of LncRNAs in Translation" Non-Coding RNA 7, no. 1: 16. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010016

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