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Volume 9
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Non-Coding RNA, Volume 9, Issue 1 (February 2023) – 16 articles

Cover Story (view full-size image): Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors of head and neck region, with a poor survival rate as a consequence of advanced-stage diagnosis and high recurrence rate. The identification of effective diagnostic and prognostic biomarkers for LSCC is crucial to guide disease management and improve clinical outcomes. A dysregulated expression of small non-coding RNAs, including microRNAs (miRNAs), has been reported in many human cancers, including LSCC, and many miRNAs have been explored for their diagnostic and prognostic potential. Using the PRISMA protocol, we searched for original papers that were focused on miRNAs and LSCC. In this systematic review, we provide an overview of the current literature on the function and the potential diagnostic and prognostic role of tissue and circulating miRNAs in LSCC. View this paper
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19 pages, 985 KiB  
Review
Non-Coding RNA-Dependent Regulation of Mitochondrial Dynamics in Cancer Pathophysiology
by Maria Eugenia Gallo Cantafio, Roberta Torcasio, Giuseppe Viglietto and Nicola Amodio
Non-Coding RNA 2023, 9(1), 16; https://doi.org/10.3390/ncrna9010016 - 20 Feb 2023
Cited by 6 | Viewed by 3694
Abstract
Mitochondria are essential organelles which dynamically change their shape and number to adapt to various environmental signals in diverse physio-pathological contexts. Mitochondrial dynamics refers to the delicate balance between mitochondrial fission (or fragmentation) and fusion, that plays a pivotal role in maintaining mitochondrial [...] Read more.
Mitochondria are essential organelles which dynamically change their shape and number to adapt to various environmental signals in diverse physio-pathological contexts. Mitochondrial dynamics refers to the delicate balance between mitochondrial fission (or fragmentation) and fusion, that plays a pivotal role in maintaining mitochondrial homeostasis and quality control, impinging on other mitochondrial processes such as metabolism, apoptosis, mitophagy, and autophagy. In this review, we will discuss how dysregulated mitochondrial dynamics can affect different cancer hallmarks, significantly impacting tumor growth, survival, invasion, and chemoresistance. Special emphasis will be given to emerging non-coding RNA molecules targeting the main fusion/fission effectors, acting as novel relevant upstream regulators of the mitochondrial dynamics rheostat in a wide range of tumors. Full article
(This article belongs to the Section Clinical Applications of Non-Coding RNA)
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15 pages, 2129 KiB  
Article
Transcriptome-Wide Analysis of microRNA–mRNA Correlations in Tissue Identifies microRNA Targeting Determinants
by Juan Manuel Trinidad-Barnech, Rafael Sebastián Fort, Guillermo Trinidad Barnech, Beatriz Garat and María Ana Duhagon
Non-Coding RNA 2023, 9(1), 15; https://doi.org/10.3390/ncrna9010015 - 13 Feb 2023
Viewed by 2689
Abstract
MicroRNAs are small RNAs that regulate gene expression through complementary base pairing with their target mRNAs. A substantial understanding of microRNA target recognition and repression mechanisms has been reached using diverse empirical and bioinformatic approaches, primarily in vitro biochemical or cell culture perturbation [...] Read more.
MicroRNAs are small RNAs that regulate gene expression through complementary base pairing with their target mRNAs. A substantial understanding of microRNA target recognition and repression mechanisms has been reached using diverse empirical and bioinformatic approaches, primarily in vitro biochemical or cell culture perturbation settings. We sought to determine if rules of microRNA target efficacy could be inferred from extensive gene expression data of human tissues. A transcriptome-wide assessment of all the microRNA–mRNA canonical interactions’ efficacy was performed using a normalized Spearman correlation (Z-score) between the abundance of the transcripts in the PRAD-TCGA dataset tissues (RNA-seq mRNAs and small RNA-seq for microRNAs, 546 samples). Using the Z-score of correlation as a surrogate marker of microRNA target efficacy, we confirmed hallmarks of microRNAs, such as repression of their targets, the hierarchy of preference for gene regions (3′UTR > CDS > 5′UTR), and seed length (6 mer < 7 mer < 8 mer), as well as the contribution of the 3′-supplementary pairing at nucleotides 13–16 of the microRNA. Interactions mediated by 6 mer + supplementary showed similar inferred repression as 7 mer sites, suggesting that the 6 mer + supplementary sites may be relevant in vivo. However, aggregated 7 mer-A1 seeds appear more repressive than 7 mer-m8 seeds, while similar when pairing possibilities at the 3′-supplementary sites. We then examined the 3′-supplementary pairing using 39 microRNAs with Z-score-inferred repressive 3′-supplementary interactions. The approach was sensitive to the offset of the bridge between seed and 3′-supplementary pairing sites, and the pattern of offset-associated repression found supports previous findings. The 39 microRNAs with effective repressive 3′supplementary sites show low GC content at positions 13–16. Our study suggests that the transcriptome-wide analysis of microRNA–mRNA correlations may uncover hints of microRNA targeting determinants. Finally, we provide a bioinformatic tool to identify microRNA–mRNA candidate interactions based on the sequence complementarity of the seed and 3′-supplementary regions. Full article
(This article belongs to the Section Small Non-Coding RNA)
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11 pages, 2586 KiB  
Article
LncRNA MALAT1 Regulates Hyperglycemia Induced EMT in Keratinocyte via miR-205
by Liping Zhang, George Chu-Chih Hung, Songmei Meng, Robin Evans and Junwang Xu
Non-Coding RNA 2023, 9(1), 14; https://doi.org/10.3390/ncrna9010014 - 11 Feb 2023
Cited by 4 | Viewed by 2225
Abstract
Epithelial-to-mesenchymal transition (EMT) is critical to cutaneous wound healing. When skin is injured, EMT activates and mobilizes keratinocytes toward the wound bed, therefore enabling re-epithelialization. This process becomes dysregulated in patients with diabetes mellitus (DM). Long non-coding RNAs (lncRNAs) regulate many biological processes. [...] Read more.
Epithelial-to-mesenchymal transition (EMT) is critical to cutaneous wound healing. When skin is injured, EMT activates and mobilizes keratinocytes toward the wound bed, therefore enabling re-epithelialization. This process becomes dysregulated in patients with diabetes mellitus (DM). Long non-coding RNAs (lncRNAs) regulate many biological processes. LncRNA-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) influences numerous cellular processes, including EMT. The objective of the current study is to explore the role of MALAT1 in hyperglycemia (HG)-induced EMT. The expression of MALAT1 was found to be significantly upregulated, while the expression of miR-205 was downregulated in diabetic wounds and high-glucose-treated HaCaT cells. The initiation of EMT in HaCaT cells from hyperglycemia was confirmed by a morphological change, the increased expression of CDH2, KRT10, and ACTA2, and the downregulation of CDH1. The knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). MALAT1 and miR-205 were found to modulate HG-induced EMT. MALAT1 silencing or miR-205 overexpression appears to attenuate hyperglycemia-induced EMT. Mechanistically, MALAT1 affects HG-induced EMT through binding to miR-205 and therefore inducing ZEB1, a critical transcription factor for EMT. In summary, lncRNA MALAT1 is involved in the hyperglycemia-induced EMT of human HaCaT cells. This provides a new perspective on the pathogenesis of diabetic wounds. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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11 pages, 1302 KiB  
Systematic Review
Circulating MicroRNAs as Specific Biomarkers in Atrial Fibrillation: A Meta-Analysis
by Antônio da Silva Menezes Junior, Lara Cristina Ferreira, Laura Júlia Valentim Barbosa, Daniela de Melo e Silva, Vera Aparecida Saddi and Antonio Márcio Teodoro Cordeiro Silva
Non-Coding RNA 2023, 9(1), 13; https://doi.org/10.3390/ncrna9010013 - 9 Feb 2023
Cited by 12 | Viewed by 2310
Abstract
Atrial fibrillation (AF) is the most frequently occurring supraventricular arrhythmia. Although microRNAs (miRNAs) have been associated with AF pathogenesis, standard protocols for quantifying and selecting specific miRNAs for clinical use as biomarkers should be optimized. In this study, we evaluated the clinical application [...] Read more.
Atrial fibrillation (AF) is the most frequently occurring supraventricular arrhythmia. Although microRNAs (miRNAs) have been associated with AF pathogenesis, standard protocols for quantifying and selecting specific miRNAs for clinical use as biomarkers should be optimized. In this study, we evaluated the clinical application of miRNAs as biomarkers for the prognosis and diagnosis of AF. Literature searches were conducted on PubMed, Cochrane Library, and EMBASE. We included prospective or retrospective observational studies that had been published as of 14 February 2022; our main objective was to analyze the relationship between circulating miRNAs and AF. The data were extracted using the descriptors “Atrial fibrillation AND miRNA”, “Atrial fibrillation AND diagnostic AND miRNA”, and “Atrial fibrillation AND prognosis AND miRNA”. No filters were applied for period delimitation, type of publication, or language. Studies using samples isolated from blood plasma and TaqMan and RT-qPCR for detecting and quantifying miRNAs were selected, and those that used atrial tissue samples were excluded. We identified 272 articles and excluded 102 duplicated articles. Two authors independently read the titles and abstracts of 170 out of 272 articles and selected 56 potential articles, 6 of which were selected for final review. Our analysis revealed a significant association between AF and miR-4798 [OR = 1.90 (95% CI 1.45–2.47)], AF and miRNA-133a [2.77 (2.73–2.82)], AF and miRNA-150 [3.77 (1.50–9.46); I2 = 70%], AF and miRNA-21 [2.23 (1.20–4.17); I2 = 99%], AF and hsa-miRNA4443 [2.32 (2.20–2.44)], and AF and miR-20a-5p [3.67 (1.42–9.49)]. The association between miRNAs and AF showed an OR of 2.51 [95% CI 1.99–3.16; I2 = 99%]. Our meta-analysis demonstrated that circulating miRNAs are potential biomarkers of AF, as they exhibit stable expression post–sample collection. In addition to regulating cellular processes, such as proliferation, differentiation, development, and cell death, miRNAs were found to be linked to arrhythmia development. Full article
(This article belongs to the Section Detection and Biomarkers of Non-Coding RNA)
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22 pages, 1674 KiB  
Review
Functional Relevance of the Long Intergenic Non-Coding RNA Regulator of Reprogramming (Linc-ROR) in Cancer Proliferation, Metastasis, and Drug Resistance
by José A. Peña-Flores, Diego Enríquez-Espinoza, Daniela Muela-Campos, Alexis Álvarez-Ramírez, Angel Sáenz, Andrés A. Barraza-Gómez, Kenia Bravo, Marvin E. Estrada-Macías and Karla González-Alvarado
Non-Coding RNA 2023, 9(1), 12; https://doi.org/10.3390/ncrna9010012 - 31 Jan 2023
Cited by 4 | Viewed by 3503
Abstract
Cancer is responsible for more than 10 million deaths every year. Metastasis and drug resistance lead to a poor survival rate and are a major therapeutic challenge. Substantial evidence demonstrates that an increasing number of long non-coding RNAs are dysregulated in cancer, including [...] Read more.
Cancer is responsible for more than 10 million deaths every year. Metastasis and drug resistance lead to a poor survival rate and are a major therapeutic challenge. Substantial evidence demonstrates that an increasing number of long non-coding RNAs are dysregulated in cancer, including the long intergenic non-coding RNA, regulator of reprogramming (linc-ROR), which mostly exerts its role as an onco-lncRNA acting as a competing endogenous RNA that sequesters micro RNAs. Although the properties of linc-ROR in relation to some cancers have been reviewed in the past, active research appends evidence constantly to a better comprehension of the role of linc-ROR in different stages of cancer. Moreover, the molecular details and some recent papers have been omitted or partially reported, thus the importance of this review aimed to contribute to the up-to-date understanding of linc-ROR and its implication in cancer tumorigenesis, progression, metastasis, and chemoresistance. As the involvement of linc-ROR in cancer is elucidated, an improvement in diagnostic and prognostic tools could promote and advance in targeted and specific therapies in precision oncology. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Clinical Implications of Non-coding RNAs in Cancer)
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11 pages, 1770 KiB  
Article
miRinGO: Prediction of Biological Processes Indirectly Targeted by Human microRNAs
by Mohammed Sayed and Juw Won Park
Non-Coding RNA 2023, 9(1), 11; https://doi.org/10.3390/ncrna9010011 - 22 Jan 2023
Cited by 4 | Viewed by 2739
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that are known for their role in the post-transcriptional regulation of target genes. Typically, their functions are predicted by first identifying their target genes and then finding biological processes enriched in these targets. Current tools for miRNA [...] Read more.
MicroRNAs (miRNAs) are small non-coding RNAs that are known for their role in the post-transcriptional regulation of target genes. Typically, their functions are predicted by first identifying their target genes and then finding biological processes enriched in these targets. Current tools for miRNA functional analysis use only genes with physical binding sites as their targets and exclude other genes that are indirectly targeted transcriptionally through transcription factors. Here, we introduce a method to predict gene ontology (GO) annotations indirectly targeted by microRNAs. The proposed method resulted in better performance in predicting known miRNA-GO term associations compared to the canonical approach. To facilitate miRNA GO enrichment analysis, we developed an R Shiny application, miRinGO, that is freely available online at GitHub. Full article
(This article belongs to the Special Issue Methods and Tools in RNA Biology)
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15 pages, 1944 KiB  
Review
Computational Methods to Study DNA:DNA:RNA Triplex Formation by lncRNAs
by Timothy Warwick, Ralf P. Brandes and Matthias S. Leisegang
Non-Coding RNA 2023, 9(1), 10; https://doi.org/10.3390/ncrna9010010 - 21 Jan 2023
Cited by 14 | Viewed by 4196
Abstract
Long non-coding RNAs (lncRNAs) impact cell function via numerous mechanisms. In the nucleus, interactions between lncRNAs and DNA and the consequent formation of non-canonical nucleic acid structures seems to be particularly relevant. Along with interactions between single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA), [...] Read more.
Long non-coding RNAs (lncRNAs) impact cell function via numerous mechanisms. In the nucleus, interactions between lncRNAs and DNA and the consequent formation of non-canonical nucleic acid structures seems to be particularly relevant. Along with interactions between single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA), such as R-loops, ssRNA can also interact with double-stranded DNA (dsDNA) to form DNA:DNA:RNA triplexes. A major challenge in the study of DNA:DNA:RNA triplexes is the identification of the precise RNA component interacting with specific regions of the dsDNA. As this is a crucial step towards understanding lncRNA function, there exist several computational methods designed to predict these sequences. This review summarises the recent progress in the prediction of triplex formation and highlights important DNA:DNA:RNA triplexes. In particular, different prediction tools (Triplexator, LongTarget, TRIPLEXES, Triplex Domain Finder, TriplexFFP, TriplexAligner and Fasim-LongTarget) will be discussed and their use exemplified by selected lncRNAs, whose DNA:DNA:RNA triplex forming potential was validated experimentally. Collectively, these tools revealed that DNA:DNA:RNA triplexes are likely to be numerous and make important contributions to gene expression regulation. Full article
(This article belongs to the Special Issue Methods and Tools in RNA Biology)
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25 pages, 1139 KiB  
Systematic Review
Diagnostic and Prognostic Value of microRNAs in Patients with Laryngeal Cancer: A Systematic Review
by Elisabetta Broseghini, Daria Maria Filippini, Laura Fabbri, Roberta Leonardi, Andi Abeshi, Davide Dal Molin, Matteo Fermi, Manuela Ferracin and Ignacio Javier Fernandez
Non-Coding RNA 2023, 9(1), 9; https://doi.org/10.3390/ncrna9010009 - 19 Jan 2023
Cited by 5 | Viewed by 3261
Abstract
Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors of the head and neck region, with a poor survival rate (5-year overall survival 50–80%) as a consequence of an advanced-stage diagnosis and high recurrence rate. Tobacco smoking and alcohol [...] Read more.
Laryngeal squamous cell cancer (LSCC) is one of the most common malignant tumors of the head and neck region, with a poor survival rate (5-year overall survival 50–80%) as a consequence of an advanced-stage diagnosis and high recurrence rate. Tobacco smoking and alcohol abuse are the main risk factors of LSCC development. An early diagnosis of LSCC, a prompt detection of recurrence and a more precise monitoring of the efficacy of different treatment modalities are currently needed to reduce the mortality. Therefore, the identification of effective diagnostic and prognostic biomarkers for LSCC is crucial to guide disease management and improve clinical outcomes. In the past years, a dysregulated expression of small non-coding RNAs, including microRNAs (miRNAs), has been reported in many human cancers, including LSCC, and many miRNAs have been explored for their diagnostic and prognostic potential and proposed as biomarkers. We searched electronic databases for original papers that were focused on miRNAs and LSCC, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. According to the outcome, 566 articles were initially screened, of which 177 studies were selected and included in the analysis. In this systematic review, we provide an overview of the current literature on the function and the potential diagnostic and prognostic role of tissue and circulating miRNAs in LSCC. Full article
(This article belongs to the Special Issue Women’s Special Issue Series: Noncoding RNAs and Diseases)
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2 pages, 169 KiB  
Editorial
Acknowledgment to the Reviewers of Non-Coding RNA in 2022
by Non-Coding RNA Editorial Office
Non-Coding RNA 2023, 9(1), 8; https://doi.org/10.3390/ncrna9010008 - 13 Jan 2023
Viewed by 1248
Abstract
High-quality academic publishing is built on rigorous peer review [...] Full article
17 pages, 14020 KiB  
Article
A Novel Cis-Regulatory lncRNA, Kalnc2, Downregulates Kalrn Protein-Coding Transcripts in Mouse Neuronal Cells
by Muneesh Pal, Divya Chaubey, Mohit Tanwar and Beena Pillai
Non-Coding RNA 2023, 9(1), 7; https://doi.org/10.3390/ncrna9010007 - 13 Jan 2023
Cited by 1 | Viewed by 2958
Abstract
The KALRN gene encodes several multi-domain protein isoforms that localize to neuronal synapses, conferring the ability to grow and retract dendritic spines and shaping axonal outgrowth, dendrite morphology, and dendritic spine re-modeling. The KALRN genomic locus is implicated in several neurodevelopmental and neuropsychiatric [...] Read more.
The KALRN gene encodes several multi-domain protein isoforms that localize to neuronal synapses, conferring the ability to grow and retract dendritic spines and shaping axonal outgrowth, dendrite morphology, and dendritic spine re-modeling. The KALRN genomic locus is implicated in several neurodevelopmental and neuropsychiatric diseases, including autism, schizophrenia, bipolar disease, and intellectual disability. We have previously shown that a novel brain-specific long non-coding RNA (lncRNA) arising from the 5′ end of the kalrna gene, called durga, regulates neuronal morphology in zebrafish. Here, we characterized mammalian Kalrn loci, annotating and experimentally validating multiple novel non-coding RNAs, including linear and circular variants. Comparing the mouse and human loci, we show that certain non-coding RNAs and Kalrn protein-coding isoforms arising from the locus show similar expression dynamics during development. In humans, mice, and zebrafish, the 5′ end of the Kalrn locus gives rise to a chromatin-associated lncRNA that is present in adult ovaries, besides being expressed during brain development and enriched in certain regions of the adult brain. Ectopic expression of this lncRNA led to the downregulation of all the major Kalrn mRNA isoforms. We propose that this lncRNA arising from the 5′ end of the Kalrn locus is functionally the mammalian ortholog of zebrafish lncRNA durga. Full article
(This article belongs to the Section Long Non-Coding RNA)
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11 pages, 2279 KiB  
Communication
Long Non-Coding RNA Expression in Alpha-1 Antitrypsin Deficient Monocytes Pre- and Post-AAT Augmentation Therapy
by Stephen G. J. Smith and Catherine M. Greene
Non-Coding RNA 2023, 9(1), 6; https://doi.org/10.3390/ncrna9010006 - 10 Jan 2023
Cited by 2 | Viewed by 1757
Abstract
Long non-coding RNAs (lncRNAs) regulate gene expression. Their expression in alpha-1 antitrypsin (AAT) deficiency has not been investigated. Treatment of AAT deficiency involves infusion of plasma-purified AAT and this augmentation therapy has previously been shown to alter microRNA expression in monocytes of AAT-deficient [...] Read more.
Long non-coding RNAs (lncRNAs) regulate gene expression. Their expression in alpha-1 antitrypsin (AAT) deficiency has not been investigated. Treatment of AAT deficiency involves infusion of plasma-purified AAT and this augmentation therapy has previously been shown to alter microRNA expression in monocytes of AAT-deficient (ZZ) individuals. Here, we assess the effect of AAT augmentation therapy on the lncRNA expression profile in ZZ monocytes. Peripheral blood monocytes were isolated from ZZ individuals pre (Day 0)- and post (Day 2)-AAT augmentation therapy. Arraystar lncRNA microarray profiling was performed; a total of 17,761 lncRNAs were detectable across all samples. The array identified 7509 lncRNAs with differential expression post-augmentation therapy, 3084 were increased and 4425 were decreased (fold change ≥ 2). Expression of many of these lncRNAs were similarly altered in ZZ monocytes treated ex vivo with 27.5 μM AAT for 4 h. These properties may contribute to the manifold effects of AAT augmentation therapy. Full article
(This article belongs to the Special Issue Women’s Special Issue Series: Noncoding RNAs and Diseases)
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17 pages, 3328 KiB  
Article
Epigenetic Regulation of HIV-1 Sense and Antisense Transcription in Response to Latency-Reversing Agents
by Rui Li, Isabella Caico, Ziyan Xu, Mohammad Shameel Iqbal and Fabio Romerio
Non-Coding RNA 2023, 9(1), 5; https://doi.org/10.3390/ncrna9010005 - 10 Jan 2023
Cited by 6 | Viewed by 2957
Abstract
Nucleosomes positioned on the HIV-1 5′ long terminal repeat (LTR) regulate sense transcription as well as the establishment and maintenance of latency. A negative-sense promoter (NSP) in the 3′ LTR expresses antisense transcripts with coding and non-coding activities. Previous studies identified cis-acting [...] Read more.
Nucleosomes positioned on the HIV-1 5′ long terminal repeat (LTR) regulate sense transcription as well as the establishment and maintenance of latency. A negative-sense promoter (NSP) in the 3′ LTR expresses antisense transcripts with coding and non-coding activities. Previous studies identified cis-acting elements that modulate NSP activity. Here, we used the two chronically infected T cell lines, ACH-2 and J1.1, to investigate epigenetic regulation of NSP activity. We found that histones H3 and H4 are present on the 3′ LTR in both cell lines. Following treatment with histone deacetylase inhibitors (HDACi), the levels of H3K27Ac increased and histone occupancy declined. HDACi treatment also led to increased levels of RNA polymerase II (RNPII) at NSP, and antisense transcription was induced with similar kinetics and to a similar extent as 5′ LTR-driven sense transcription. We also detected H3K9me2 and H3K27me3 on NSP, along with the enzymes responsible for these epigenetic marks, namely G9a and EZH2, respectively. Treatment with their respective inhibitors had little or no effect on RNPII occupancy at the two LTRs, but it induced both sense and antisense transcription. Moreover, the increased expression of antisense transcripts in response to treatment with a panel of eleven latency-reversing agents closely paralleled and was often greater than the effect on sense transcripts. Thus, HIV-1 sense and antisense RNA expression are both regulated via acetylation and methylation of lysine 9 and 27 on histone H3. Since HIV-1 antisense transcripts act as non-coding RNAs promoting epigenetic silencing of the 5′ LTR, our results suggest that the limited efficacy of latency-reversing agents in the context of ‘shock and kill’ cure strategies may be due to concurrent induction of antisense transcripts thwarting their effect on sense transcription. Full article
(This article belongs to the Special Issue Insights into Antisense Long Non-Coding RNAs Metabolism and Expression)
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18 pages, 1819 KiB  
Article
Deciphering the Role of microRNA Mediated Regulation of Coronin 1C in Glioblastoma Development and Metastasis
by Denis Mustafov, Emmanouil Karteris and Maria Braoudaki
Non-Coding RNA 2023, 9(1), 4; https://doi.org/10.3390/ncrna9010004 - 4 Jan 2023
Cited by 5 | Viewed by 3248
Abstract
Glioblastoma multiforme (GBM) is a highly heterogenic and malignant brain tumour with a median survival of 15 months. The initial identification of primary glioblastomas is often challenging. Coronin 1C (CORO1C) is a key player in actin rearrangement and cofilin dynamics, as well as [...] Read more.
Glioblastoma multiforme (GBM) is a highly heterogenic and malignant brain tumour with a median survival of 15 months. The initial identification of primary glioblastomas is often challenging. Coronin 1C (CORO1C) is a key player in actin rearrangement and cofilin dynamics, as well as enhancing the processes of neurite overgrowth and migration of brain tumour cells. Different bioinformatic databases were accessed to measure CORO1C expression at the mRNA and protein level in normal and malignant brains. CORO1C expression was observed in brain regions which have retained high synaptic plasticity and myelination properties. CORO1C was also expressed mainly within the hippocampus formation, including the Cornu Ammonis (CA) fields: CA1–CA4. Higher expression was also noticed in paediatric GBM in comparison to their adult counterparts. Pediatric cell populations were observed to have an increased log2 expression of CORO1C. Furthermore, 62 miRNAs were found to target the CORO1C gene. Of these, hsa-miR-34a-5p, hsa-miR-512-3p, hsa-miR-136-5p, hsa-miR-206, hsa-miR-128-3p, and hsa-miR-21-5p have shown to act as tumour suppressors or oncomiRs in different neoplasms, including GBM. The elevated expression of CORO1C in high grade metastatic brain malignancies, including GBM, suggests that this protein could have a clinical utility as a biomarker linked to an unfavorable outcome. Full article
(This article belongs to the Topic MicroRNA: Mechanisms of Action, Physio-Pathological Implications, and Disease Biomarkers)
(This article belongs to the Section Small Non-Coding RNA)
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14 pages, 2492 KiB  
Article
Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain
by Allison Kirchner, Fabien Dachet, Leonard Lipovich and Jeffrey A. Loeb
Non-Coding RNA 2023, 9(1), 3; https://doi.org/10.3390/ncrna9010003 - 4 Jan 2023
Cited by 5 | Viewed by 2591
Abstract
The human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than protein-coding [...] Read more.
The human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than protein-coding genes in evolution. Patients who have surgery for drug-resistant epilepsy are subjected to extensive electrical recordings of the brain tissue that is subsequently removed in order to treat their epilepsy. Precise localization of brain tissues with distinct electrical properties offers a rare opportunity to explore the effects of brain activity on gene expression. Here, we identified 231 co-regulated, activity-dependent lncRNAs within the human MAPK signaling cascade. Six lncRNAs, four of which were antisense to known protein-coding genes, were further examined because of their high expression and potential impact on the disease phenotype. Using a model of repeated depolarizations in human neuronal-like cells (Sh-SY5Y), we show that five out of six lncRNAs were electrical activity-dependent, with three of four antisense lncRNAs having reciprocal expression patterns relative to their protein-coding gene partners. Some were directly regulated by MAPK signaling, while others effectively downregulated the expression of the protein-coding genes encoded on the opposite strands of their genomic loci. These lncRNAs, therefore, likely contribute to highly evolved and primate-specific human brain regulatory functions that could be therapeutically modulated to treat epilepsy. Full article
(This article belongs to the Special Issue Selected Papers from IEEE BIBM 2021 Workshop on Long Non-coding RNAs: Mechanism, Function, and Computational Analysis (BIBM-LncRNA))
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15 pages, 3780 KiB  
Article
High Throughput FISH Screening Identifies Small Molecules That Modulate Oncogenic lncRNA MALAT1 via GSK3B and hnRNPs
by Nina Zablowsky, Lydia Farack, Sven Rofall, Jan Kramer, Hanna Meyer, Duy Nguyen, Alexander K. C. Ulrich, Benjamin Bader and Patrick Steigemann
Non-Coding RNA 2023, 9(1), 2; https://doi.org/10.3390/ncrna9010002 - 3 Jan 2023
Cited by 3 | Viewed by 4016
Abstract
Traditionally, small molecule-based drug discovery has mainly focused on proteins as the drug target. Opening RNA as an additional target space for small molecules offers the possibility to therapeutically modulate disease-driving non-coding RNA targets as well as mRNA of otherwise undruggable protein targets. [...] Read more.
Traditionally, small molecule-based drug discovery has mainly focused on proteins as the drug target. Opening RNA as an additional target space for small molecules offers the possibility to therapeutically modulate disease-driving non-coding RNA targets as well as mRNA of otherwise undruggable protein targets. MALAT1 is a highly conserved long-noncoding RNA whose overexpression correlates with poor overall patient survival in some cancers. We report here a fluorescence in-situ hybridization-based high-content imaging screen to identify small molecules that modulate the oncogenic lncRNA MALAT1 in a cellular setting. From a library of FDA approved drugs and known bioactive molecules, we identified two compounds, including Niclosamide, an FDA-approved drug, that lead to a rapid decrease of MALAT1 nuclear levels with good potency. Mode-of-action studies suggest a novel cellular regulatory pathway that impacts MALAT1 lncRNA nuclear levels by GSK3B activation and the involvement of the RNA modulating family of heterogenous nuclear ribonucleoproteins (hnRNPs). This study is the basis for the identification of novel targets that lead to a reduction of the oncogenic lncRNA MALAT1 in a cancer setting. Full article
(This article belongs to the Section Long Non-Coding RNA)
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20 pages, 1993 KiB  
Review
FLVCR1-AS1 and FBXL19-AS1: Two Putative lncRNA Candidates in Multiple Human Cancers
by Mohsen Sheykhhasan, Hamid Tanzadehpanah, Amirhossein Ahmadieh Yazdi, Hanie Mahaki, Reihaneh Seyedebrahimi, Mohammad Akbari, Hamed Manoochehri, Naser Kalhor and Paola Dama
Non-Coding RNA 2023, 9(1), 1; https://doi.org/10.3390/ncrna9010001 - 22 Dec 2022
Cited by 9 | Viewed by 2936
Abstract
(1) Background: Mounting evidence supports the idea that one of the most critical agents in controlling gene expression could be long non-coding RNAs (lncRNAs). Upregulation of lncRNA is observed in the different processes related to pathologies, such as tumor occurrence and development. Among [...] Read more.
(1) Background: Mounting evidence supports the idea that one of the most critical agents in controlling gene expression could be long non-coding RNAs (lncRNAs). Upregulation of lncRNA is observed in the different processes related to pathologies, such as tumor occurrence and development. Among the crescent number of lncRNAs discovered, FLVCR1-AS1 and FBXL19-AS1 have been identified as oncogenes in many cancer progression and prognosis types, including cholangiocarcinoma, gastric cancer, glioma and glioblastoma, hepatocellular carcinoma, lung cancer, ovarian cancer, breast cancer, colorectal cancer, and osteosarcoma. Therefore, abnormal FBXL19-AS1 and FLVCR1-AS1 expression affect a variety of cellular activities, including metastasis, aggressiveness, and proliferation; (2) Methods: This study was searched via PubMed and Google Scholar databases until May 2022; (3) Results: FLVCR1-AS1 and FBXL19-AS1 participate in tumorigenesis and have an active role in impacting several signaling pathways that regulate cell proliferation, migration, invasion, metastasis, and EMT; (4) Conclusions: Our review focuses on the possible molecular mechanisms in a variety of cancers regulated by FLVCR1-AS1 and FBXL19-AS1. It is not surprising that there has been significant interest in the possibility that these lncRNAs might be used as biomarkers for diagnosis or as a target to improve a broader range of cancers in the future. Full article
(This article belongs to the Special Issue The Importance of Non-coding RNAs in Epithelial Cancers)
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