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Volume 6, September

Non-Coding RNA, Volume 6, Issue 4 (December 2020) – 10 articles

Cover Story (view full-size image): Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts with a minimal length of 200 nucleotides. They are involved in physiological processes such as cell differentiation, as well as in pathophysiological processes such as cancer. There are numerous examples of deregulated lncRNAs in various types of tumors, thereby contributing to different hallmarks of cancer, such as angiogenesis. To exceed a tumor size with a diameter of more than 2 mm, the formation of blood vessels is vital to supply the tumor with sufficient nutrients and oxygen. Recently, studies have reported that lncRNAs regulate tumor angiogenesis by directly or indirectly influencing numerous pathways by binding proteins, interacting with other RNA transcripts or modulating the tumor microenvironment. View this paper
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Communication
Human Cytomegalovirus-Encoded microRNAs Can Be Found in Saliva Samples from Renal Transplant Recipients
Non-Coding RNA 2020, 6(4), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040050 - 18 Dec 2020
Cited by 2 | Viewed by 2029
Abstract
Human cytomegalovirus (HCMV) infections are common following renal transplantation and may have long-lasting effects. HCMV can be measured directly by viral DNA or indirectly via host immune responses. HCMV-encoded microRNA (miRNA) may alter the pathobiology of HCMV infections and contribute to the progression [...] Read more.
Human cytomegalovirus (HCMV) infections are common following renal transplantation and may have long-lasting effects. HCMV can be measured directly by viral DNA or indirectly via host immune responses. HCMV-encoded microRNA (miRNA) may alter the pathobiology of HCMV infections and contribute to the progression of HCMV disease. HCMV-encoded miRNAs can be detected in blood but have not been sought in saliva. We investigated saliva samples from 32 renal transplant recipients (RTR) and 12 seropositive healthy controls for whom immunological data was available. Five HCMV-encoded miRNAs (miR-UL112-5p, miR-US5-2-3p, miR-UL36, miR-US25-2-3p and miR-UL22A) were sought using primer probe assays. HCMV miRNA species were detected in saliva from 15 RTR and 3 healthy controls, with miR-US5-2-3p most commonly detected. The presence of HCMV miRNAs associated with increased T-cell responses to HCMV IE-1 in RTR, suggesting a link with frequent reactivations of HCMV. Full article
(This article belongs to the Special Issue Non-coding RNAs in Biology of Viruses)
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Review
The lncRNA Toolkit: Databases and In Silico Tools for lncRNA Analysis
Non-Coding RNA 2020, 6(4), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040049 - 16 Dec 2020
Cited by 5 | Viewed by 2886
Abstract
Long non-coding RNAs (lncRNAs) are a rapidly expanding field of research, with many new transcripts identified each year. However, only a small subset of lncRNAs has been characterized functionally thus far. To aid investigating the mechanisms of action by which new lncRNAs act, [...] Read more.
Long non-coding RNAs (lncRNAs) are a rapidly expanding field of research, with many new transcripts identified each year. However, only a small subset of lncRNAs has been characterized functionally thus far. To aid investigating the mechanisms of action by which new lncRNAs act, bioinformatic tools and databases are invaluable. Here, we review a selection of computational tools and databases for the in silico analysis of lncRNAs, including tissue-specific expression, protein coding potential, subcellular localization, structural conformation, and interaction partners. The assembled lncRNA toolkit is aimed primarily at experimental researchers as a useful starting point to guide wet-lab experiments, mainly containing multi-functional, user-friendly interfaces. With more and more new lncRNA analysis tools available, it will be essential to provide continuous updates and maintain the availability of key software in the future. Full article
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Article
Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas
Non-Coding RNA 2020, 6(4), 48; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040048 - 15 Dec 2020
Cited by 3 | Viewed by 1987
Abstract
Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer [...] Read more.
Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer and reduction of mortality (~20%). However, a sizable fraction of patients (30–50%) with early stage disease still experience relapse and an adverse prognosis. Thus, the identification of effective prognostic biomarkers in stage I lung cancer is nowadays paramount. Here, we applied a multi-tiered approach relying on coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients (TCGA-LUAD, n = 510), which enabled us to identify prognostic miRNA signatures in stage I lung adenocarcinoma. Such signatures showed high accuracy (AUC ranging between 0.79 and 0.85) in scoring aggressive disease. Importantly, using a network-based approach we rewired miRNA-mRNA regulatory networks, identifying a minimal signature of 7 miRNAs, which was validated in a cohort of FFPE lung adenocarcinoma samples (CSS, n = 44) and controls a variety of genes overlapping with cancer relevant pathways. Our results further demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine. Full article
(This article belongs to the Collection Feature Papers in Non-coding RNA)
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Review
Deep Learning in LncRNAome: Contribution, Challenges, and Perspectives
Non-Coding RNA 2020, 6(4), 47; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040047 - 30 Nov 2020
Cited by 3 | Viewed by 2090
Abstract
Long non-coding RNAs (lncRNA), the pervasively transcribed part of the mammalian genome, have played a significant role in changing our protein-centric view of genomes. The abundance of lncRNAs and their diverse roles across cell types have opened numerous avenues for the research community [...] Read more.
Long non-coding RNAs (lncRNA), the pervasively transcribed part of the mammalian genome, have played a significant role in changing our protein-centric view of genomes. The abundance of lncRNAs and their diverse roles across cell types have opened numerous avenues for the research community regarding lncRNAome. To discover and understand lncRNAome, many sophisticated computational techniques have been leveraged. Recently, deep learning (DL)-based modeling techniques have been successfully used in genomics due to their capacity to handle large amounts of data and produce relatively better results than traditional machine learning (ML) models. DL-based modeling techniques have now become a choice for many modeling tasks in the field of lncRNAome as well. In this review article, we summarized the contribution of DL-based methods in nine different lncRNAome research areas. We also outlined DL-based techniques leveraged in lncRNAome, highlighting the challenges computational scientists face while developing DL-based models for lncRNAome. To the best of our knowledge, this is the first review article that summarizes the role of DL-based techniques in multiple areas of lncRNAome. Full article
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Article
LINC00473 as an Immediate Early Gene under the Control of the EGR1 Transcription Factor
Non-Coding RNA 2020, 6(4), 46; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040046 - 12 Nov 2020
Viewed by 1881
Abstract
Immediate early genes play an essential role in cellular responses to different stimuli. Many of them are transcription factors that regulate the secondary response gene expression. Non-coding RNAs may also be involved in this regulatory cascade. In fact, they are emerging as key [...] Read more.
Immediate early genes play an essential role in cellular responses to different stimuli. Many of them are transcription factors that regulate the secondary response gene expression. Non-coding RNAs may also be involved in this regulatory cascade. In fact, they are emerging as key actors of gene expression regulation, and evidence suggests that their dysregulation may underly pathological states. We previously took a snapshot of both coding and long non-coding RNAs differentially expressed in neuronal cells after brain-derived neurotrophic factor stimulation. Among these, the transcription factor EGR1 (a well-known immediate early gene) and LINC00473 (a primate-specific long non-coding RNA) that has emerged as an interesting RNA candidate involved in neuronal function and in cancer. In this work, we demonstrated that LINC00473 gene expression kinetics resembled that of immediate early genes in SH-SY5Y and HEK293T cells under different cell stimulation conditions. Moreover, we showed that the expression of LINC00473 is under the control of the transcription factor EGR1, providing evidence for an interesting functional relationship in neuron function. Full article
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Review
Seeing Is Believing: Visualizing Circular RNAs
Non-Coding RNA 2020, 6(4), 45; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040045 - 11 Nov 2020
Cited by 3 | Viewed by 2272
Abstract
Advancement in the RNA sequencing techniques has discovered hundreds of thousands of circular RNAs (circRNAs) in humans. However, the physiological function of most of the identified circRNAs remains unexplored. Recent studies have established that spliceosomal machinery and RNA-binding proteins modulate circRNA biogenesis. Furthermore, [...] Read more.
Advancement in the RNA sequencing techniques has discovered hundreds of thousands of circular RNAs (circRNAs) in humans. However, the physiological function of most of the identified circRNAs remains unexplored. Recent studies have established that spliceosomal machinery and RNA-binding proteins modulate circRNA biogenesis. Furthermore, circRNAs have been implicated in regulating crucial cellular processes by interacting with various proteins and microRNAs. However, there are several challenges in understanding the mechanism of circRNA biogenesis, transport, and their interaction with cellular factors to regulate cellular events because of their low abundance and sequence similarity with linear RNA. Addressing these challenges requires systematic studies that directly visualize the circRNAs in cells at single-molecule resolution along with the molecular regulators. In this review, we present the design, benefits, and weaknesses of RNA imaging techniques such as single-molecule RNA fluorescence in situ hybridization and BaseScope in fixed cells and fluorescent RNA aptamers in live-cell imaging of circRNAs. Furthermore, we propose the potential use of molecular beacons, multiply labeled tetravalent RNA imaging probes, and Cas-derived systems to visualize circRNAs. Full article
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Review
Emerging Roles of Long Noncoding RNAs in the Cytoplasmic Milieu
Non-Coding RNA 2020, 6(4), 44; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040044 - 09 Nov 2020
Cited by 8 | Viewed by 2507
Abstract
While the important functions of long noncoding RNAs (lncRNAs) in nuclear organization are well documented, their orchestrating and architectural roles in the cytoplasmic environment have long been underestimated. However, recently developed fractionation and proximity labelling approaches have shown that a considerable proportion of [...] Read more.
While the important functions of long noncoding RNAs (lncRNAs) in nuclear organization are well documented, their orchestrating and architectural roles in the cytoplasmic environment have long been underestimated. However, recently developed fractionation and proximity labelling approaches have shown that a considerable proportion of cellular lncRNAs is exported into the cytoplasm and associates nonrandomly with proteins in the cytosol and organelles. The functions of these lncRNAs range from the control of translation and mitochondrial metabolism to the anchoring of cellular components on the cytoskeleton and regulation of protein degradation at the proteasome. In the present review, we provide an overview of the functions of lncRNAs in cytoplasmic structures and machineries und discuss their emerging roles in the coordination of the dense intracellular milieu. It is becoming apparent that further research into the functions of these lncRNAs will lead to an improved understanding of the spatiotemporal organization of cytoplasmic processes during homeostasis and disease. Full article
(This article belongs to the Collection Feature Papers in Non-coding RNA)
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Review
NEAT1 and Paraspeckles in Cancer Development and Chemoresistance
Non-Coding RNA 2020, 6(4), 43; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040043 - 30 Oct 2020
Cited by 2 | Viewed by 2242
Abstract
Non-coding RNA were previously thought to be biologically useless molecules arising from simple transcriptional noise. These are now known to be an integral part of cellular biology and pathology. The wide range of RNA molecules have a diverse range of structures, functions, and [...] Read more.
Non-coding RNA were previously thought to be biologically useless molecules arising from simple transcriptional noise. These are now known to be an integral part of cellular biology and pathology. The wide range of RNA molecules have a diverse range of structures, functions, and mechanisms of action. However, structural long non-coding RNAs (lncRNAs) are a particular class of ncRNA that are proving themselves more and more important in cellular biology, as the exact structures that such RNAs form and stabilise become more understood. Nuclear Enriched Abundant Transcript 1 (NEAT1) is a specific structural RNA emerging as a critical component in the progress and development of cancer. NEAT1 forms part of multiple biological pathways, acting through a diverse group of mechanisms. The most important of these is the formation of the paraspeckle, through which it can influence the stability of a tumour to develop resistance to drugs. This review will thus cover the range of effects by which NEAT1 interacts with cancer progression in order to describe the various roles of NEAT1 in chemoresistance, as well as to identify drug targets that protein research alone could not provide. Full article
(This article belongs to the Special Issue Non-coding RNAs Involved in Cancer Chemoresistance)
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Review
Involvement of Long Non-Coding RNAs (lncRNAs) in Tumor Angiogenesis
Non-Coding RNA 2020, 6(4), 42; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040042 - 25 Sep 2020
Cited by 9 | Viewed by 2550
Abstract
Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts with a minimal length of 200 nucleotides. They are involved in various biological processes such as cell differentiation, apoptosis, as well as in pathophysiological processes. Numerous studies considered that frequently deregulated lncRNAs contribute [...] Read more.
Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts with a minimal length of 200 nucleotides. They are involved in various biological processes such as cell differentiation, apoptosis, as well as in pathophysiological processes. Numerous studies considered that frequently deregulated lncRNAs contribute to all hallmarks of cancer including metastasis, drug resistance, and angiogenesis. Angiogenesis, the formation of new blood vessels, is crucial for a tumor to receive sufficient amounts of nutrients and oxygen and therefore, to grow and exceed in its size over the diameter of 2 mm. In this review, the regulatory mechanisms of lncRNAs are described, which influence tumor angiogenesis by directly or indirectly regulating oncogenic pathways, interacting with other transcripts such as microRNAs (miRNAs) or modulating the tumor microenvironment. Further, angiogenic lncRNAs occurring in several cancer types such as liver, gastrointestinal cancer, or brain tumors are summarized. Growing evidence on the influence of lncRNAs on tumor angiogenesis verified these transcripts as potential predictive or diagnostic biomarkers or therapeutic targets of anti-angiogenesis treatment. However, there are many unsolved questions left which are pointed out in this review, hence driving comprehensive research in this area is necessary to enable an effective use of lncRNAs as either therapeutic molecules or diagnostic targets in cancer. Full article
(This article belongs to the Collection Feature Papers in Non-coding RNA)
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Article
FuncPEP: A Database of Functional Peptides Encoded by Non-Coding RNAs
Non-Coding RNA 2020, 6(4), 41; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6040041 - 23 Sep 2020
Cited by 4 | Viewed by 2623
Abstract
Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less [...] Read more.
Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids. The sequences encoding these peptides are known as small open reading frames (smORFs), many initiating with the traditional AUG start codon but terminating with atypical stop codons, suggesting a different biogenesis. The ncRNA-encoded peptides (ncPEPs) are gradually becoming appreciated as a new class of functional molecules that contribute to diverse cellular processes, and are deregulated in different diseases contributing to pathogenesis. As multiple publications have identified unique ncPEPs, we appreciated the need for assembling a new web resource that could gather information about these functional ncPEPs. We developed FuncPEP, a new database of functional ncRNA encoded peptides, containing all experimentally validated and functionally characterized ncPEPs. Currently, FuncPEP includes a comprehensive annotation of 112 functional ncPEPs and specific details regarding the ncRNA transcripts that encode these peptides. We believe that FuncPEP will serve as a platform for further deciphering the biologic significance and medical use of ncPEPs. The link for FuncPEP database can be found at the end of the Introduction Section. Full article
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