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15 pages, 2651 KiB

Open AccessArticle

miR-1285-3p Controls Colorectal Cancer Proliferation and Escape from Apoptosis through DAPK2

by Lidia Villanova, Chiara Barbini, Cristina Piccolo, Alessandra Boe, Ruggero De Maria and Micol Eleonora Fiori

Int. J. Mol. Sci. 2020, 21(7), 2423; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072423 - 31 Mar 2020

Cited by 13 | Viewed by 3089

Abstract

MicroRNAs are tiny but powerful regulators of gene expression at the post-transcriptional level. Aberrant expression of oncogenic and tumor-suppressor microRNAs has been recognized as a common feature of human cancers. Colorectal cancer represents a major clinical challenge in the developed world and the [...] Read more.

MicroRNAs are tiny but powerful regulators of gene expression at the post-transcriptional level. Aberrant expression of oncogenic and tumor-suppressor microRNAs has been recognized as a common feature of human cancers. Colorectal cancer represents a major clinical challenge in the developed world and the design of innovative therapeutic approaches relies on the identification of novel biological targets. Here, we perform a functional screening in colorectal cancer cells using a library of locked nucleic acid (LNA)-modified anti-miRs in order to unveil putative oncogenic microRNAs whose inhibition yields a cytotoxic effect. We identify miR-1285-3p and further explore the effect of its targeting in both commercial cell lines and primary colorectal cancer stem cells, finding induction of cell cycle arrest and apoptosis. We show that DAPK2, a known tumor-suppressor, is a novel miR-1285 target and mediates both the anti-proliferative and the pro-apoptotic effects of miR-1285 depletion. Altogether, our findings uncover a novel oncogenic microRNA in colorectal cancer and lay the foundation for further studies aiming at the development of possible therapeutic strategies based on miR-1285 targeting. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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14 pages, 2326 KiB

Open AccessArticle

MiR&moRe2: A Bioinformatics Tool to Characterize microRNAs and microRNA-Offset RNAs from Small RNA-Seq Data

by Enrico Gaffo, Michele Bortolomeazzi, Andrea Bisognin, Piero Di Battista, Federica Lovisa, Lara Mussolin and Stefania Bortoluzzi

Int. J. Mol. Sci. 2020, 21(5), 1754; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051754 - 04 Mar 2020

Cited by 10 | Viewed by 4110

Abstract

MicroRNA-offset RNAs (moRNAs) are microRNA-like small RNAs generated by microRNA precursors. To date, little is known about moRNAs and bioinformatics tools to inspect their expression are still missing. We developed miR&moRe2, the first bioinformatics method to consistently characterize microRNAs, moRNAs, and their isoforms [...] Read more.

MicroRNA-offset RNAs (moRNAs) are microRNA-like small RNAs generated by microRNA precursors. To date, little is known about moRNAs and bioinformatics tools to inspect their expression are still missing. We developed miR&moRe2, the first bioinformatics method to consistently characterize microRNAs, moRNAs, and their isoforms from small RNA sequencing data. To illustrate miR&moRe2 discovery power, we applied it to several published datasets. MoRNAs identified by miR&moRe2 were in agreement with previous research findings. Moreover, we observed that moRNAs and new microRNAs predicted by miR&moRe2 were downregulated upon the silencing of the microRNA-biogenesis pathway. Further, in a sizeable dataset of human blood cell populations, tens of novel miRNAs and moRNAs were discovered, some of them with significantly varied expression levels among the cell types. Results demonstrate that miR&moRe2 is a valid tool for a comprehensive study of small RNAs generated from microRNA precursors and could help to investigate their biogenesis and function. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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19 pages, 5395 KiB

Open AccessArticle

Transcriptome Analysis Reveals Long Intergenic Non-Coding RNAs Contributed to Intramuscular Fat Content Differences between Yorkshire and Wei Pigs

by Qianqian Li, Ziying Huang, Wenjuan Zhao, Mengxun Li and Changchun Li

Int. J. Mol. Sci. 2020, 21(5), 1732; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051732 - 03 Mar 2020

Cited by 24 | Viewed by 3316

Abstract

Intramuscular fat (IMF) content is closely related to various meat traits, such as tenderness, juiciness, and flavor. The IMF content varies considerably among pig breeds with different genetic backgrounds. Long intergenic non-coding RNAs (lincRNAs) have been widely identified in many species and found [...] Read more.

Intramuscular fat (IMF) content is closely related to various meat traits, such as tenderness, juiciness, and flavor. The IMF content varies considerably among pig breeds with different genetic backgrounds. Long intergenic non-coding RNAs (lincRNAs) have been widely identified in many species and found to be an important class of regulators that can participate in multiple biological processes. However, the mechanism behind lincRNAs regulation of pig IMF content remains unknown and requires further study. In our study, we identified a total of 156 lincRNAs in the longissimus dorsi muscle of Wei (fat-type) and Yorkshire (lean-type) pigs using previously published data. These identified lincRNAs have shorter transcript length, longer exon length, lower exon number, and lower expression level as compared with protein-coding transcripts. We predicted potential target genes (PTGs) that are potentially regulated by lincRNAs in cis or trans regulation. Gene ontology and pathway analyses indicated that many potential lincRNAs target genes are involved in IMF-related processes or pathways, such as fatty acid catabolic process and adipocytokine signaling pathway. In addition, we analyzed quantitative trait locus (QTL) sites that differentially expressed lincRNAs (DE lincRNAs) between Wei and Yorkshire pigs co-localized. The QTL sites where DE lincRNAs co-localize are mostly related to IMF content. Furthermore, we constructed a co-expressed network between DE lincRNAs and their differentially expressed PTGs (DEPTGs). On the basis of their expression levels, we suggest that many DE lincRNAs can affect IMF development by positively or negatively regulating their PTGs. This study identified and analyzed some lincRNAs- and PTGs-related IMF development of the two pig breeds and provided new insight into research on the roles of lincRNAs in the two types of breeds. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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26 pages, 4858 KiB

Open AccessArticle

Secreted Factors and EV-miRNAs Orchestrate the Healing Capacity of Adipose Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis

by Enrico Ragni, Carlotta Perucca Orfei, Paola De Luca, Alessandra Colombini, Marco Viganò and Laura de Girolamo

Int. J. Mol. Sci. 2020, 21(5), 1582; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051582 - 26 Feb 2020

Cited by 46 | Viewed by 4174

Abstract

Mesenchymal stem cells (MSCs) derived from adipose tissue and used either as expanded cells or minimally manipulated cell preparations showed positive clinical outcomes in regenerative medicine approaches based on tissue restoration and inflammation control, like in osteoarthritis (OA). Recently, MSCs’ healing capacity has [...] Read more.

Mesenchymal stem cells (MSCs) derived from adipose tissue and used either as expanded cells or minimally manipulated cell preparations showed positive clinical outcomes in regenerative medicine approaches based on tissue restoration and inflammation control, like in osteoarthritis (OA). Recently, MSCs’ healing capacity has been ascribed to the large array of soluble factors, including soluble cytokines/chemokines and miRNAs conveyed within extracellular vesicles (EVs). Therefore, in this study, 200 secreted cytokines, chemokines and growth factors via ELISA, together with EV-embedded miRNAs via high-throughput techniques, were scored in adipose-derived MSCs (ASCs) cultivated under inflammatory conditions, mimicking OA synovial fluid. Both factors (through most abundantly expressed TIMP1, TIMP2, PLG and CTSS) and miRNAs (miR-24-3p, miR-222-3p and miR-193b-3p) suggested a strong capacity for ASCs to reduce matrix degradation activities, as those activated in OA cartilage, and switch synovial macrophages, often characterized by an M1 inflammatory polarization, towards an M2 phenotype. Moreover, the crucial importance of selecting the target tissue is discussed, showing how a focused search may greatly improve potency prediction and explain clinical outcomes. In conclusion, herein presented data shed light about the way ASCs regulate cell homeostasis and regenerative pathways in an OA-resembling environment, therefore suggesting a rationale for the use of MSC-enriched clinical products, such as stromal vascular fraction and microfragmented adipose tissue, in joint pathologies. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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16 pages, 2779 KiB

Open AccessArticle

miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model

by Greta Streleckiene, Ruta Inciuraite, Simonas Juzenas, Violeta Salteniene, Ruta Steponaitiene, Ugne Gyvyte, Gediminas Kiudelis, Marcis Leja, Paulius Ruzgys, Saulius Satkauskas, Eugenija Kupcinskiene, Sabine Franke, Cosima Thon, Alexander Link, Juozas Kupcinskas and Jurgita Skieceviciene

Int. J. Mol. Sci. 2020, 21(3), 877; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030877 - 29 Jan 2020

Cited by 28 | Viewed by 3836

Abstract

Gastric cancer (GC) is one of the most common and lethal gastrointestinal malignancies worldwide. Many studies have shown that development of GC and other malignancies is mainly driven by alterations of cellular signaling pathways. MicroRNAs (miRNAs) are small noncoding molecules that function as [...] Read more.

Gastric cancer (GC) is one of the most common and lethal gastrointestinal malignancies worldwide. Many studies have shown that development of GC and other malignancies is mainly driven by alterations of cellular signaling pathways. MicroRNAs (miRNAs) are small noncoding molecules that function as tumor-suppressors or oncogenes, playing an essential role in a variety of fundamental biological processes. In order to understand the functional relevance of miRNA dysregulation, studies analyzing their target genes are of major importance. Here, we chose to analyze two miRNAs, miR-20b and miR-451a, shown to be deregulated in many different malignancies, including GC. Deregulated expression of miR-20b and miR-451a was determined in GC cell lines and the INS-GAS mouse model. Using Western Blot and luciferase reporter assay we determined that miR-20b directly regulates expression of PTEN and TXNIP, and miR-451a: CAV1 and TSC1. Loss-of-function experiments revealed that down-regulation of miR-20b and up-regulation of miR-451a expression exhibits an anti-tumor effect in vitro (miR-20b: reduced viability, colony formation, increased apoptosis rate, and miR-451a: reduced colony forming ability). To summarize, the present study identified that expression of miR-20b and miR-451a are deregulated in vitro and in vivo and have a tumor suppressive role in GC through regulation of the PI3K/AKT/mTOR signaling pathway. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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14 pages, 1581 KiB

Open AccessArticle

Docker4Circ: A Framework for the Reproducible Characterization of circRNAs from RNA-Seq Data

by Giulio Ferrero, Nicola Licheri, Lucia Coscujuela Tarrero, Carlo De Intinis, Valentina Miano, Raffaele Adolfo Calogero, Francesca Cordero, Michele De Bortoli and Marco Beccuti

Int. J. Mol. Sci. 2020, 21(1), 293; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010293 - 31 Dec 2019

Cited by 9 | Viewed by 3124

Abstract

Recent improvements in cost-effectiveness of high-throughput technologies has allowed RNA sequencing of total transcriptomes suitable for evaluating the expression and regulation of circRNAs, a relatively novel class of transcript isoforms with suggested roles in transcriptional and post-transcriptional gene expression regulation, as well as [...] Read more.

Recent improvements in cost-effectiveness of high-throughput technologies has allowed RNA sequencing of total transcriptomes suitable for evaluating the expression and regulation of circRNAs, a relatively novel class of transcript isoforms with suggested roles in transcriptional and post-transcriptional gene expression regulation, as well as their possible use as biomarkers, due to their deregulation in various human diseases. A limited number of integrated workflows exists for prediction, characterization, and differential expression analysis of circRNAs, none of them complying with computational reproducibility requirements. We developed Docker4Circ for the complete analysis of circRNAs from RNA-Seq data. Docker4Circ runs a comprehensive analysis of circRNAs in human and model organisms, including: circRNAs prediction; classification and annotation using six public databases; back-splice sequence reconstruction; internal alternative splicing of circularizing exons; alignment-free circRNAs quantification from RNA-Seq reads; and differential expression analysis. Docker4Circ makes circRNAs analysis easier and more accessible thanks to: (i) its R interface; (ii) encapsulation of computational tasks into docker images; (iii) user-friendly Java GUI Interface availability; and (iv) no need of advanced bash scripting skills for correct use. Furthermore, Docker4Circ ensures a reproducible analysis since all its tasks are embedded into a docker image following the guidelines provided by Reproducible Bioinformatics Project. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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19 pages, 2432 KiB

Open AccessArticle

Secondary Structural Model of Human MALAT1 Reveals Multiple Structure–Function Relationships

by Phillip J. McCown, Matthew C. Wang, Luc Jaeger and Jessica A. Brown

Int. J. Mol. Sci. 2019, 20(22), 5610; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225610 - 09 Nov 2019

Cited by 42 | Viewed by 5500

Abstract

Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an abundant nuclear-localized long noncoding RNA (lncRNA) that has significant roles in cancer. While the interacting partners and evolutionary sequence conservation of MALAT1 have been examined, much of the structure of MALAT1 is unknown. Here, [...] Read more.

Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an abundant nuclear-localized long noncoding RNA (lncRNA) that has significant roles in cancer. While the interacting partners and evolutionary sequence conservation of MALAT1 have been examined, much of the structure of MALAT1 is unknown. Here, we propose a hypothetical secondary structural model for 8425 nucleotides of human MALAT1 using three experimental datasets that probed RNA structures in vitro and in various human cell lines. Our model indicates that approximately half of human MALAT1 is structured, forming 194 helices, 13 pseudoknots, five structured tetraloops, nine structured internal loops, and 13 intramolecular long-range interactions that give rise to several multiway junctions. Evolutionary conservation and covariation analyses support 153 of 194 helices in 51 mammalian MALAT1 homologs and 42 of 194 helices in 53 vertebrate MALAT1 homologs, thereby identifying an evolutionarily conserved core that likely has important functional roles in mammals and vertebrates. Data mining revealed that RNA modifications, somatic cancer-associated mutations, and single-nucleotide polymorphisms may induce structural rearrangements that sequester or expose binding sites for several cancer-associated microRNAs. Our findings reveal new mechanistic leads into the roles of MALAT1 by identifying several intriguing structure–function relationships in which the dynamic structure of MALAT1 underlies its biological functions. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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18 pages, 3341 KiB

Open AccessArticle

Transcriptome Analysis Implicates Involvement of Long Noncoding RNAs in Cytoplasmic Male Sterility and Fertility Restoration in Cotton

by Bingbing Zhang, Xuexian Zhang, Meng Zhang, Liping Guo, Tingxiang Qi, Hailin Wang, Huini Tang, Xiuqin Qiao, Kashif Shahzad, Chaozhu Xing and Jianyong Wu

Int. J. Mol. Sci. 2019, 20(22), 5530; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225530 - 06 Nov 2019

Cited by 11 | Viewed by 2626

Abstract

The cytoplasmic male sterility (CMS)/restorer-of-fertility system is an important tool to exploit heterosis during commercially hybrid seed production. The importance of long noncoding RNAs (lncRNAs) in plant development is recognized, but few analyses of lncRNAs during anther development of three-line hybrid cotton (CMS-D2 [...] Read more.

The cytoplasmic male sterility (CMS)/restorer-of-fertility system is an important tool to exploit heterosis during commercially hybrid seed production. The importance of long noncoding RNAs (lncRNAs) in plant development is recognized, but few analyses of lncRNAs during anther development of three-line hybrid cotton (CMS-D2 line A, maintainer line B, restorer-of-fertility line R) have been reported. Here, we performed transcriptome sequencing during anther development in three-line hybrid cotton. A total of 80,695 lncRNAs were identified, in which 43,347 and 44,739 lncRNAs were differentially expressed in A–B and A–R comparisons, respectively. These lncRNAs represent functional candidates involved in CMS and fertility restoration. GO analysis indicated that cellular hormone metabolic processes and oxidation–reduction reaction processes might be involved in CMS, and cellular component morphogenesis and small molecular biosynthetic processes might participate in fertility restoration. Additionally, 63 lncRNAs were identified as putative precursors of 35 miRNAs, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed a similar expression pattern to RNA-seq data. Furthermore, construction of lncRNA regulatory networks indicated that several miRNA–lncRNA–mRNA networks might be involved in CMS and fertility restoration. Our findings provide systematic identification of lncRNAs during anther development and lays a solid foundation for the regulatory mechanisms and utilization in hybrid cotton breeding. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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12 pages, 1483 KiB

Open AccessArticle

Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD

by Marianna Lucafò, Letizia Pugnetti, Matteo Bramuzzo, Debora Curci, Alessia Di Silvestre, Annalisa Marcuzzi, Alberta Bergamo, Stefano Martelossi, Vincenzo Villanacci, Anna Bozzola, Moris Cadei, Sara De Iudicibus, Giuliana Decorti and Gabriele Stocco

Int. J. Mol. Sci. 2019, 20(21), 5280; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215280 - 24 Oct 2019

Cited by 26 | Viewed by 2783

Abstract

Background: The long non-coding RNA (lncRNA) growth arrest–specific transcript 5 (GAS5) seems to be involved in the regulation of mediators of tissue injury, in particular matrix metalloproteinases (MMPs), implicated in the pathogenesis of inflammatory bowel disease (IBD). We investigated the role [...] Read more.

Background: The long non-coding RNA (lncRNA) growth arrest–specific transcript 5 (GAS5) seems to be involved in the regulation of mediators of tissue injury, in particular matrix metalloproteinases (MMPs), implicated in the pathogenesis of inflammatory bowel disease (IBD). We investigated the role of GAS5 in regulating MMP2 and MMP9 expression in pediatric patients with IBD and in vitro. Methods: In total, 25 IBD patients were enrolled: For each patient paired inflamed and non-inflamed biopsies were collected. RNA was extracted and GAS5, MMP2, and MMP9 were quantified by TaqMan assay. The expression of GAS5 and MMPs was also determined in the human monocytic THP1 cells differentiated into macrophages and stimulated with lipopolysaccharide (LPS). The function of GAS5 was assessed by overexpressing the lncRNA and evaluating the MMPs levels. Results: Real-time PCR results demonstrated a downregulation of GAS5 and an upregulation of both MMPs in inflamed tissues. In vitro data confirmed the trend observed in patients for the three genes: The stimulation with LPS promoted a downregulation of GAS5 while an increase of MMPs was observed. Overexpression experiments showed that higher levels of GAS5 lead to a decrease of both enzymes. Conclusion: These results provide new information about the role of GAS5 in IBD: The lncRNA could mediate tissue damage by modulating the expression of MMPs. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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16 pages, 1956 KiB

Open AccessArticle

Functional Prediction of Candidate MicroRNAs for CRC Management Using in Silico Approach

by Adewale Oluwaseun Fadaka, Ashley Pretorius and Ashwil Klein

Int. J. Mol. Sci. 2019, 20(20), 5190; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20205190 - 19 Oct 2019

Cited by 6 | Viewed by 2826

Abstract

Approximately 30–50% of malignant growths can be prevented by avoiding risk factors and implementing evidence-based strategies. Colorectal cancer (CRC) accounted for the second most common cancer and the third most common cause of cancer death worldwide. This cancer subtype can be reduced by [...] Read more.

Approximately 30–50% of malignant growths can be prevented by avoiding risk factors and implementing evidence-based strategies. Colorectal cancer (CRC) accounted for the second most common cancer and the third most common cause of cancer death worldwide. This cancer subtype can be reduced by early detection and patients’ management. In this study, the functional roles of the identified microRNAs were determined using an in silico pipeline. Five microRNAs identified using an in silico approach alongside their seven target genes from our previous study were used as datasets in this study. Furthermore, the secondary structure and the thermodynamic energies of the microRNAs were revealed by Mfold algorithm. The triplex binding ability of the oligonucleotide with the target promoters were analyzed by Trident. Finally, evolutionary stage-specific somatic events and co-expression analysis of the target genes in CRC were analyzed by SEECancer and GeneMANIA plugin in Cytoscape. Four of the five microRNAs have the potential to form more than one secondary structure. The ranges of the observed/expected ratio of CpG dinucleotides of these genes range from 0.60 to 1.22. Three of the candidate microRNA were capable of forming multiple triplexes along with three of the target mRNAs. Four of the total targets were involved in either early or metastatic stage-specific events while three other genes were either a product of antecedent or subsequent events of the four genes implicated in CRC. The secondary structure of the candidate microRNAs can be used to explain the different degrees of genetic regulation in CRC due to their conformational role to modulate target interaction. Furthermore, due to the regulation of important genes in the CRC pathway and the enrichment of the microRNA with triplex binding sites, they may be a useful diagnostic biomarker for the disease subtype. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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13 pages, 822 KiB

Open AccessArticle

MicroRNA Biogenesis Pathway Genes Are Deregulated in Colorectal Cancer

by Petra Vychytilova-Faltejskova, Alena Svobodova Kovarikova, Tomas Grolich, Vladimir Prochazka, Katerina Slaba, Tana Machackova, Jana Halamkova, Marek Svoboda, Zdenek Kala, Igor Kiss and Ondrej Slaby

Int. J. Mol. Sci. 2019, 20(18), 4460; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184460 - 10 Sep 2019

Cited by 14 | Viewed by 2899

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Each step of their production and maturation has to be strictly regulated, as any disruption of control mechanisms may lead to cancer. Thus, we have measured the expression of 19 genes involved [...] Read more.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Each step of their production and maturation has to be strictly regulated, as any disruption of control mechanisms may lead to cancer. Thus, we have measured the expression of 19 genes involved in miRNAs biogenesis pathway in tumor tissues of 239 colorectal cancer (CRC) patients, 17 CRC patients with liver metastases and 239 adjacent tissues using real-time PCR. Subsequently, the expression of analyzed genes was correlated with the clinical-pathological features as well as with the survival of patients. In total, significant over-expression of all analyzed genes was observed in tumor tissues as well as in liver metastases except for LIN28A/B. Furthermore, it was shown that the deregulated levels of some of the analyzed genes significantly correlate with tumor stage, grade, location, size and lymph node positivity. Finally, high levels of DROSHA and TARBP2 were associated with shorter disease-free survival, while the over-expression of XPO5, TNRC6A and DDX17 was detected in tissues of patients with shorter overall survival and poor prognosis. Our data indicate that changed levels of miRNA biogenesis genes may contribute to origin as well as progression of CRC; thus, these molecules could serve as potential therapeutic targets. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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15 pages, 245 KiB

Open AccessArticle

Analysis of the Association Between MicroRNA Biogenesis Gene Polymorphisms and Venous Thromboembolism in Koreans

by Eun Ju Ko, Eo Jin Kim, Jung Oh Kim, Jung Hoon Sung, Han Sung Park, Chang Soo Ryu, Jisu Oh, So Young Chong, Doyeun Oh and Nam Keun Kim

Int. J. Mol. Sci. 2019, 20(15), 3771; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20153771 - 01 Aug 2019

Cited by 3 | Viewed by 2663

Abstract

Venous thromboembolism (VTE) involves the formation of a blood clot, typically in the deep veins of the leg or arm (deep vein thrombosis), which then travels via the circulatory system and ultimately lodges in the lungs, resulting in pulmonary embolism. A number of [...] Read more.

Venous thromboembolism (VTE) involves the formation of a blood clot, typically in the deep veins of the leg or arm (deep vein thrombosis), which then travels via the circulatory system and ultimately lodges in the lungs, resulting in pulmonary embolism. A number of microRNAs (miRNAs) are well-known regulators of thrombosis and thrombolysis, and mutations in miRNA biogenesis genes, such as DICER1, DROSHA have been implicated in miRNA synthesis and function. We investigated the genetic association between polymorphisms in four miRNA biogenesis genes, DICER1 rs3742330A > G, DROSHA rs10719T > C, RAN rs14035C > T and XPO5 rs11077A > C, and VTE in 503 Koreans: 300 controls and 203 patients. Genotyping was assessed with polymerase chain reaction-restriction fragment length polymorphism assays. We detected associations between polymorphisms in RAN and XPO5 and VTE prevalence (RAN rs14035CC + CT versus TT: p = 0.018; XPO5 rs11077AA + AC versus CC: p < 0.001). Analysis of allele combinations of all four polymorphisms (DICER1, DROSHA, RAN, XPO5) revealed that A-T-T-A was associated with decreased VTE prevalence (p = 0.0002), and A-T-C-C was associated with increased VTE prevalence (p = 0.027). Moreover, in subjects with provoked VTE, the DROSHA rs10719T > C, polymorphism was associated with increased disease prevalence (TT versus TC + CC: p < 0.039). Our study demonstrates that RAN and XPO5 polymorphisms are associated with risk for VTE in Korean subjects. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

Review

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19 pages, 816 KiB

Open AccessReview

Psychiatric Disorders and lncRNAs: A Synaptic Match

by Francesco Rusconi, Elena Battaglioli and Marco Venturin

Int. J. Mol. Sci. 2020, 21(9), 3030; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093030 - 25 Apr 2020

Cited by 26 | Viewed by 5124

Abstract

Psychiatric disorders represent a heterogeneous class of multifactorial mental diseases whose origin entails a pathogenic integration of genetic and environmental influences. Incidence of these pathologies is dangerously high, as more than 20% of the Western population is affected. Despite the diverse origins of [...] Read more.

Psychiatric disorders represent a heterogeneous class of multifactorial mental diseases whose origin entails a pathogenic integration of genetic and environmental influences. Incidence of these pathologies is dangerously high, as more than 20% of the Western population is affected. Despite the diverse origins of specific molecular dysfunctions, these pathologies entail disruption of fine synaptic regulation, which is fundamental to behavioral adaptation to the environment. The synapses, as functional units of cognition, represent major evolutionary targets. Consistently, fine synaptic tuning occurs at several levels, involving a novel class of molecular regulators known as long non-coding RNAs (lncRNAs). Non-coding RNAs operate mainly in mammals as epigenetic modifiers and enhancers of proteome diversity. The prominent evolutionary expansion of the gene number of lncRNAs in mammals, particularly in primates and humans, and their preferential neuronal expression does represent a driving force that enhanced the layering of synaptic control mechanisms. In the last few years, remarkable alterations of the expression of lncRNAs have been reported in psychiatric conditions such as schizophrenia, autism, and depression, suggesting unprecedented mechanistic insights into disruption of fine synaptic tuning underlying severe behavioral manifestations of psychosis. In this review, we integrate literature data from rodent pathological models and human evidence that proposes the biology of lncRNAs as a promising field of neuropsychiatric investigation. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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17 pages, 1805 KiB

Open AccessReview

piRNAs in Gastric Cancer: A New Approach Towards Translational Research

by Gleyce Fonseca Cabral, Jhully Azevedo dos Santos Pinheiro, Amanda Ferreira Vidal, Sidney Santos and Ândrea Ribeiro-dos-Santos

Int. J. Mol. Sci. 2020, 21(6), 2126; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062126 - 19 Mar 2020

Cited by 24 | Viewed by 5926

Abstract

Background: Gastric cancer is currently the third leading cause of cancer-related deaths worldwide, usually diagnosed at late stages. The development of new biomarkers to improve its prevention and patient management is critical for disease control. piRNAs are small regulatory RNAs important for gene [...] Read more.

Background: Gastric cancer is currently the third leading cause of cancer-related deaths worldwide, usually diagnosed at late stages. The development of new biomarkers to improve its prevention and patient management is critical for disease control. piRNAs are small regulatory RNAs important for gene silencing mechanisms, mainly associated with the silencing of transposable elements. piRNA pathways may also be involved in gene regulation and the deregulation of piRNAs may be an important factor in carcinogenic processes. Thus, several studies suggest piRNAs as potential cancer biomarkers. Translational studies suggest that piRNAs may regulate key genes and pathways associated with gastric cancer progression, though there is no functional annotation in piRNA databases. The impacts of genetic variants in piRNA genes and their influence in gastric cancer development remains elusive, highlighting the gap in piRNA regulatory mechanisms knowledge. Here, we discuss the current state of understanding of piRNA-mediated regulation and piRNA functions and suggest that genetic alterations in piRNA genes may affect their functionality, thus, it may be associated with gastric carcinogenesis. Conclusions: In the era of precision medicine, investigations about genetic and epigenetic mechanisms are essential to further comprehend gastric carcinogenesis and the role of piRNAs as potential biomarkers for translational research. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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25 pages, 3424 KiB

Open AccessReview

The Pervasive Role of the miR-181 Family in Development, Neurodegeneration, and Cancer

by Alessia Indrieri, Sabrina Carrella, Pietro Carotenuto, Sandro Banfi and Brunella Franco

Int. J. Mol. Sci. 2020, 21(6), 2092; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062092 - 18 Mar 2020

Cited by 90 | Viewed by 6286

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs playing a fundamental role in the regulation of gene expression. Evidence accumulating in the past decades indicate that they are capable of simultaneously modulating diverse signaling pathways involved in a variety of pathophysiological processes. In the present [...] Read more.

MicroRNAs (miRNAs) are small noncoding RNAs playing a fundamental role in the regulation of gene expression. Evidence accumulating in the past decades indicate that they are capable of simultaneously modulating diverse signaling pathways involved in a variety of pathophysiological processes. In the present review, we provide a comprehensive overview of the function of a highly conserved group of miRNAs, the miR-181 family, both in physiological as well as in pathological conditions. We summarize a large body of studies highlighting a role for this miRNA family in the regulation of key biological processes such as embryonic development, cell proliferation, apoptosis, autophagy, mitochondrial function, and immune response. Importantly, members of this family have been involved in many pathological processes underlying the most common neurodegenerative disorders as well as different solid tumors and hematological malignancies. The relevance of this miRNA family in the pathogenesis of these disorders and their possible influence on the severity of their manifestations will be discussed. A better understanding of the miR-181 family in pathological conditions may open new therapeutic avenues for devasting disorders such as neurodegenerative diseases and cancer. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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22 pages, 1440 KiB

Open AccessReview

Mitochondrial Epigenetics: Non-Coding RNAs as a Novel Layer of Complexity

by Giovanna C. Cavalcante, Leandro Magalhães, Ândrea Ribeiro-dos-Santos and Amanda F. Vidal

Int. J. Mol. Sci. 2020, 21(5), 1838; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051838 - 06 Mar 2020

Cited by 42 | Viewed by 6137

Abstract

Mitochondria are organelles responsible for several functions involved in cellular balance, including energy generation and apoptosis. For decades now, it has been well-known that mitochondria have their own genetic material (mitochondrial DNA), which is different from nuclear DNA in many ways. More recently, [...] Read more.

Mitochondria are organelles responsible for several functions involved in cellular balance, including energy generation and apoptosis. For decades now, it has been well-known that mitochondria have their own genetic material (mitochondrial DNA), which is different from nuclear DNA in many ways. More recently, studies indicated that, much like nuclear DNA, mitochondrial DNA is regulated by epigenetic factors, particularly DNA methylation and non-coding RNAs (ncRNAs). This field is now called mitoepigenetics. Additionally, it has also been established that nucleus and mitochondria are constantly communicating to each other to regulate different cellular pathways. However, little is known about the mechanisms underlying mitoepigenetics and nuclei–mitochondria communication, and also about the involvement of the ncRNAs in mitochondrial functions and related diseases. In this context, this review presents the state-of-the-art knowledge, focusing on ncRNAs as new players in mitoepigenetic regulation and discussing future perspectives of these fields. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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18 pages, 629 KiB

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Regulatory Mechanism of MicroRNA Expression in Cancer

by Zainab Ali Syeda, Siu Semar Saratu’ Langden, Choijamts Munkhzul, Mihye Lee and Su Jung Song

Int. J. Mol. Sci. 2020, 21(5), 1723; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051723 - 03 Mar 2020

Cited by 540 | Viewed by 20548

Abstract

Altered gene expression is the primary molecular mechanism responsible for the pathological processes of human diseases, including cancer. MicroRNAs (miRNAs) are virtually involved at the post-transcriptional level and bind to 3′ UTR of their target messenger RNA (mRNA) to suppress expression. Dysfunction of [...] Read more.

Altered gene expression is the primary molecular mechanism responsible for the pathological processes of human diseases, including cancer. MicroRNAs (miRNAs) are virtually involved at the post-transcriptional level and bind to 3′ UTR of their target messenger RNA (mRNA) to suppress expression. Dysfunction of miRNAs disturbs expression of oncogenic or tumor-suppressive target genes, which is implicated in cancer pathogenesis. As such, a large number of miRNAs have been found to be downregulated or upregulated in human cancers and to function as oncomiRs or oncosuppressor miRs. Notably, the molecular mechanism underlying the dysregulation of miRNA expression in cancer has been recently uncovered. The genetic deletion or amplification and epigenetic methylation of miRNA genomic loci and the transcription factor-mediated regulation of primary miRNA often alter the landscape of miRNA expression in cancer. Dysregulation of the multiple processing steps in mature miRNA biogenesis can also cause alterations in miRNA expression in cancer. Detailed knowledge of the regulatory mechanism of miRNAs in cancer is essential for understanding its physiological role and the implications of cancer-associated dysfunction and dysregulation. In this review, we elucidate how miRNA expression is deregulated in cancer, paying particular attention to the cancer-associated transcriptional and post-transcriptional factors that execute miRNA programs. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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16 pages, 876 KiB

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RNA-Sequencing Analyses of Small Bacterial RNAs and their Emergence as Virulence Factors in Host-Pathogen Interactions

by Idrissa Diallo and Patrick Provost

Int. J. Mol. Sci. 2020, 21(5), 1627; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051627 - 27 Feb 2020

Cited by 37 | Viewed by 6125

Abstract

Proteins have long been considered to be the most prominent factors regulating so-called invasive genes involved in host-pathogen interactions. The possible role of small non-coding RNAs (sRNAs), either intracellular, secreted or packaged in outer membrane vesicles (OMVs), remained unclear until recently. The advent [...] Read more.

Proteins have long been considered to be the most prominent factors regulating so-called invasive genes involved in host-pathogen interactions. The possible role of small non-coding RNAs (sRNAs), either intracellular, secreted or packaged in outer membrane vesicles (OMVs), remained unclear until recently. The advent of high-throughput RNA-sequencing (RNA-seq) techniques has accelerated sRNA discovery. RNA-seq radically changed the paradigm on bacterial virulence and pathogenicity to the point that sRNAs are emerging as an important, distinct class of virulence factors in both gram-positive and gram-negative bacteria. The potential of OMVs, as protectors and carriers of these functional, gene regulatory sRNAs between cells, has also provided an additional layer of complexity to the dynamic host-pathogen relationship. Using a non-exhaustive approach and through examples, this review aims to discuss the involvement of sRNAs, either free or loaded in OMVs, in the mechanisms of virulence and pathogenicity during bacterial infection. We provide a brief overview of sRNA origin and importance and describe the classical and more recent methods of identification that have enabled their discovery, with an emphasis on the theoretical lower limit of RNA sizes considered for RNA sequencing and bioinformatics analyses. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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21 pages, 4110 KiB

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Human Long Noncoding RNA Interactome: Detection, Characterization and Function

by Marek Kazimierczyk, Marta K. Kasprowicz, Marta E. Kasprzyk and Jan Wrzesinski

Int. J. Mol. Sci. 2020, 21(3), 1027; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031027 - 04 Feb 2020

Cited by 120 | Viewed by 18289

Abstract

The application of a new generation of sequencing techniques has revealed that most of the genome has already been transcribed. However, only a small part of the genome codes proteins. The rest of the genome "dark matter” belongs to divergent groups of non-coding [...] Read more.

The application of a new generation of sequencing techniques has revealed that most of the genome has already been transcribed. However, only a small part of the genome codes proteins. The rest of the genome "dark matter” belongs to divergent groups of non-coding RNA (ncRNA), that is not translated into proteins. There are two groups of ncRNAs, which include small and long non-coding RNAs (sncRNA and lncRNA respectively). Over the last decade, there has been an increased interest in lncRNAs and their interaction with cellular components. In this review, we presented the newest information about the human lncRNA interactome. The term lncRNA interactome refers to cellular biomolecules, such as nucleic acids, proteins, and peptides that interact with lncRNA. The lncRNA interactome was characterized in the last decade, however, understanding what role the biomolecules associated with lncRNA play and the nature of these interactions will allow us to better understand lncRNA's biological functions in the cell. We also describe a set of methods currently used for the detection of lncRNA interactome components and the analysis of their interactions. We think that such a holistic and integrated analysis of the lncRNA interactome will help to better understand its potential role in the development of organisms and cancers. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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14 pages, 2018 KiB

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Epigenetic Signaling and RNA Regulation in Cardiovascular Diseases

by Alessia Mongelli, Sandra Atlante, Tiziana Bachetti, Fabio Martelli, Antonella Farsetti and Carlo Gaetano

Int. J. Mol. Sci. 2020, 21(2), 509; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020509 - 13 Jan 2020

Cited by 19 | Viewed by 3761

Abstract

RNA epigenetics is perhaps the most recent field of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combinations whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining [...] Read more.

RNA epigenetics is perhaps the most recent field of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combinations whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes in RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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32 pages, 2073 KiB

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A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

by Enrico Alessio, Raphael Severino Bonadio, Lisa Buson, Francesco Chemello and Stefano Cagnin

Int. J. Mol. Sci. 2020, 21(1), 302; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010302 - 01 Jan 2020

Cited by 45 | Viewed by 5857

Abstract

In late 2012 it was evidenced that most of the human genome is transcribed but only a small percentage of the transcripts are translated. This observation supported the importance of non-coding RNAs and it was confirmed in several organisms. The most abundant non-translated [...] Read more.

In late 2012 it was evidenced that most of the human genome is transcribed but only a small percentage of the transcripts are translated. This observation supported the importance of non-coding RNAs and it was confirmed in several organisms. The most abundant non-translated transcripts are long non-coding RNAs (lncRNAs). In contrast to protein-coding RNAs, they show a more cell-specific expression. To understand the function of lncRNAs, it is fundamental to investigate in which cells they are preferentially expressed and to detect their subcellular localization. Recent improvements of techniques that localize single RNA molecules in tissues like single-cell RNA sequencing and fluorescence amplification methods have given a considerable boost in the knowledge of the lncRNA functions. In recent years, single-cell transcription variability was associated with non-coding RNA expression, revealing this class of RNAs as important transcripts in the cell lineage specification. The purpose of this review is to collect updated information about lncRNA classification and new findings on their function derived from single-cell analysis. We also retained useful for all researchers to describe the methods available for single-cell analysis and the databases collecting single-cell and lncRNA data. Tables are included to schematize, describe, and compare exposed concepts. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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22 pages, 1892 KiB

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The Potential Role of MicroRNA-124 in Cerebral Ischemia Injury

by Xiaolu Liu, Zhitao Feng, Lipeng Du, Yaguang Huang, Jinwen Ge, Yihui Deng and Zhigang Mei

Int. J. Mol. Sci. 2020, 21(1), 120; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010120 - 23 Dec 2019

Cited by 57 | Viewed by 7126

Abstract

Cerebral ischemia injury, the leading cause of morbidity and mortality worldwide, initiates sequential molecular and cellular pathologies that underlie ischemic encephalopathy (IE), such as ischemic stroke, Alzheimer disease (AD), Parkinson’s disease (PD), epilepsy, etc. Targeted therapeutic treatments are urgently needed to tackle the [...] Read more.

Cerebral ischemia injury, the leading cause of morbidity and mortality worldwide, initiates sequential molecular and cellular pathologies that underlie ischemic encephalopathy (IE), such as ischemic stroke, Alzheimer disease (AD), Parkinson’s disease (PD), epilepsy, etc. Targeted therapeutic treatments are urgently needed to tackle the pathological processes implicated in these neurological diseases. Recently, accumulating studies demonstrate that microRNA-124 (miR-124), the most abundant miRNA in brain tissue, is aberrant in peripheral blood and brain vascular endothelial cells following cerebral ischemia. Importantly, miR-124 regulates a variety of pathophysiological processes that are involved in the pathogenesis of age-related IE. However, the role of miR-124 has not been systematically illustrated. Paradoxically, miR-124 exerts beneficial effects in the age-related IE via regulating autophagy, neuroinflammation, oxidative stress, neuronal excitability, neurodifferentiation, Aβ deposition, and hyperphosphorylation of tau protein, while it may play a dual role via regulating apoptosis and exerts detrimental effects on synaptic plasticity and axonal growth. In the present review, we thus focus on the paradoxical roles of miR-124 in age-related IE, as well as the underlying mechanisms. A great understanding of the effects of miR-124 on the hypoxic–ischemic brain will open new avenues for therapeutic approaches to protect against cerebral ischemia injury. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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15 pages, 1370 KiB

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Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders

by Eleonora D’Ambra, Davide Capauto and Mariangela Morlando

Int. J. Mol. Sci. 2019, 20(21), 5477; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215477 - 04 Nov 2019

Cited by 51 | Viewed by 5031

Abstract

Circular RNAs (circRNAs) are a distinctive class of regulatory non-coding RNAs characterised by the presence of covalently closed ends. They are evolutionary conserved molecules, and although detected in different tissues, circRNAs resulted specifically enriched in the nervous system. Recent studies have shown that [...] Read more.

Circular RNAs (circRNAs) are a distinctive class of regulatory non-coding RNAs characterised by the presence of covalently closed ends. They are evolutionary conserved molecules, and although detected in different tissues, circRNAs resulted specifically enriched in the nervous system. Recent studies have shown that circRNAs are dynamically modulated during neuronal development and aging, that circRNAs are enriched at synaptic levels and resulted modulated after synaptic plasticity induction. This has suggested that circRNAs might play an important role in neuronal specification and activity. Despite the exact function of circRNAs is still poorly understood, emerging evidence indicates that circRNAs have important regulatory functions that might extensively contribute to the dynamic modulation of gene expression that supports neuronal pathways. More interestingly, deregulation of circRNAs expression has been linked with various pathological conditions. In this review, we describe current advances in the field of circRNA biogenesis and function in the nervous system both in physiological and in pathological conditions, and we specifically lay out their association with neurodegenerative diseases. Furthermore, we discuss the opportunity to exploit circRNAs for innovative therapeutic approaches and, due to their high stability, to use circRNAs as suitable biomarkers for diagnosis and disease progression. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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14 pages, 617 KiB

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Long Non-Coding RNAs and Related Molecular Pathways in the Pathogenesis of Epilepsy

by Chiara Villa, Marialuisa Lavitrano and Romina Combi

Int. J. Mol. Sci. 2019, 20(19), 4898; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194898 - 02 Oct 2019

Cited by 44 | Viewed by 3810

Abstract

Epilepsy represents one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system (CNS). Recurrent seizures are the cardinal clinical manifestation. Although it has been reported that the underlying pathological processes include inflammation, changes in synaptic strength, [...] Read more.

Epilepsy represents one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system (CNS). Recurrent seizures are the cardinal clinical manifestation. Although it has been reported that the underlying pathological processes include inflammation, changes in synaptic strength, apoptosis, and ion channels dysfunction, currently the pathogenesis of epilepsy is not yet completely understood. Long non-coding RNAs (lncRNAs), a class of long transcripts without protein-coding capacity, have emerged as regulatory molecules that are involved in a wide variety of biological processes. A growing number of studies reported that lncRNAs participate in the regulation of pathological processes of epilepsy and they are dysregulated during epileptogenesis. Moreover, an aberrant expression of lncRNAs linked to epilepsy has been observed both in patients and in animal models. In this review, we summarize latest advances concerning the mechanisms of action and the involvement of the most dysregulated lncRNAs in epilepsy. However, the functional roles of lncRNAs in the disease pathogenesis are still to be explored and we are only at the beginning. Additional studies are needed for the complete understanding of the underlying mechanisms and they would result in the use of lncRNAs as diagnostic biomarkers and novel therapeutic targets. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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19 pages, 754 KiB

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Human Circulating miRNAs Real-time qRT-PCR-based Analysis: An Overview of Endogenous Reference Genes Used for Data Normalization

by Simone Donati, Simone Ciuffi and Maria L. Brandi

Int. J. Mol. Sci. 2019, 20(18), 4353; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184353 - 05 Sep 2019

Cited by 76 | Viewed by 6193

Abstract

miRNAs are small non-coding RNAs of about 18–25 nucleotides that negatively regulate gene expression at the post-transcriptional level. It was reported that a deregulation of their expression patterns correlates to the onset and progression of various diseases. Recently, these molecules have been identified [...] Read more.

miRNAs are small non-coding RNAs of about 18–25 nucleotides that negatively regulate gene expression at the post-transcriptional level. It was reported that a deregulation of their expression patterns correlates to the onset and progression of various diseases. Recently, these molecules have been identified in a great plethora of biological fluids, and have also been proposed as potential diagnostic and prognostic biomarkers. Actually, real time quantitative polymerase chain reaction is the most widely used approach for circulating miRNAs (c-miRNAs) expression profiling. Nevertheless, the debate on the choice of the most suitable endogenous reference genes for c-miRNAs expression levels normalization is still open. In this regard, numerous research groups are focusing their efforts upon identifying specific, highly stable, endogenous c-mRNAs. The aim of this review is to provide an overview on the reference genes currently used in the study of various pathologies, offering to researchers the opportunity to select the appropriate molecules for c-miRNA levels normalization, when their choosing is based upon literature data. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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13 pages, 895 KiB

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Circular RNAs: Biogenesis, Mechanism, and Function in Human Cancers

by Xing Zhao, Yujie Cai and Jianzhen Xu

Int. J. Mol. Sci. 2019, 20(16), 3926; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20163926 - 13 Aug 2019

Cited by 159 | Viewed by 6986

Abstract

CircRNAs are a class of noncoding RNA species with a circular configuration that is formed by either typical spliceosome-mediated or lariat-type splicing. The expression of circRNAs is usually abnormal in many cancers. Several circRNAs have been demonstrated to play important roles in carcinogenesis. [...] Read more.

CircRNAs are a class of noncoding RNA species with a circular configuration that is formed by either typical spliceosome-mediated or lariat-type splicing. The expression of circRNAs is usually abnormal in many cancers. Several circRNAs have been demonstrated to play important roles in carcinogenesis. In this review, we will first provide an introduction of circRNAs biogenesis, especially the regulation of circRNA by RNA-binding proteins, then we will focus on the recent findings of circRNA molecular mechanisms and functions in cancer development. Finally, some open questions are also discussed. Full article

(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)

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