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ncRNA
Volume 10
Issue 4
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Non-Coding RNA, Volume 10, Issue 4 (August 2024) – 9 articles

Cover Story (view full-size image): We have developed a novel amplification-free analytical platform to detect and quantify microRNA cancer biomarkers at concentration levels found in liquid biopsies and at approximately +/−20% accuracy across all concentrations. This platform uses total RNA isolated from the biospecimen as the microRNA source and the MinION nanopore device from Oxford Nanopore Technologies (ONT) for sensing. Detection and quantification of the target microRNA are enabled by a complementary oligo probe enhanced with osmium tags. Copies of microRNA cancer biomarkers show approximate 1.8-fold overexpression, with no data overlap between healthy and cancer samples. Once microRNA copies are normalized to the same total RNA content, they appear independent of the biospecimen, suggesting that urine may replace blood withdrawal. View this paper
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13 pages, 317 KiB  
Review
Predicting the Effect of miRNA on Gene Regulation to Foster Translational Multi-Omics Research—A Review on the Role of Super-Enhancers
by Sarmistha Das and Shesh N. Rai
Non-Coding RNA 2024, 10(4), 45; https://doi.org/10.3390/ncrna10040045 - 15 Aug 2024
Viewed by 1084
Abstract
Gene regulation is crucial for cellular function and homeostasis. It involves diverse mechanisms controlling the production of specific gene products and contributing to tissue-specific variations in gene expression. The dysregulation of genes leads to disease, emphasizing the need to understand these mechanisms. Computational [...] Read more.
Gene regulation is crucial for cellular function and homeostasis. It involves diverse mechanisms controlling the production of specific gene products and contributing to tissue-specific variations in gene expression. The dysregulation of genes leads to disease, emphasizing the need to understand these mechanisms. Computational methods have jointly studied transcription factors (TFs), microRNA (miRNA), and messenger RNA (mRNA) to investigate gene regulatory networks. However, there remains a knowledge gap in comprehending gene regulatory networks. On the other hand, super-enhancers (SEs) have been implicated in miRNA biogenesis and function in recent experimental studies, in addition to their pivotal roles in cell identity and disease progression. However, statistical/computational methodologies harnessing the potential of SEs in deciphering gene regulation networks remain notably absent. However, to understand the effect of miRNA on mRNA, existing statistical/computational methods could be updated, or novel methods could be developed by accounting for SEs in the model. In this review, we categorize existing computational methods that utilize TF and miRNA data to understand gene regulatory networks into three broad areas and explore the challenges of integrating enhancers/SEs. The three areas include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in the identification of therapeutic targets and disease biomarkers. We believe that constructing statistical/computational models that dissect the role of SEs in predicting the effect of miRNA on gene regulation is crucial for tackling these challenges. Full article
(This article belongs to the Special Issue Perspectives and Innovations in Non-Coding RNA Bioinformatics)
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19 pages, 2347 KiB  
Review
Noncoding RNA-Mediated Epigenetic Regulation in Hepatic Stellate Cells of Liver Fibrosis
by Ruoyu Gao and Jingwei Mao
Non-Coding RNA 2024, 10(4), 44; https://doi.org/10.3390/ncrna10040044 - 7 Aug 2024
Viewed by 984
Abstract
Liver fibrosis is a significant contributor to liver-related disease mortality on a global scale. Despite this, there remains a dearth of effective therapeutic interventions capable of reversing this condition. Consequently, it is imperative that we gain a comprehensive understanding of the underlying mechanisms [...] Read more.
Liver fibrosis is a significant contributor to liver-related disease mortality on a global scale. Despite this, there remains a dearth of effective therapeutic interventions capable of reversing this condition. Consequently, it is imperative that we gain a comprehensive understanding of the underlying mechanisms driving liver fibrosis. In this regard, the activation of hepatic stellate cells (HSCs) is recognized as a pivotal factor in the development and progression of liver fibrosis. The role of noncoding RNAs (ncRNAs) in epigenetic regulation of HSCs transdifferentiation into myofibroblasts has been established, providing new insights into gene expression changes during HSCs activation. NcRNAs play a crucial role in mediating the epigenetics of HSCs, serving as novel regulators in the pathogenesis of liver fibrosis. As research on epigenetics expands, the connection between ncRNAs involved in HSCs activation and epigenetic mechanisms becomes more evident. These changes in gene regulation have attracted considerable attention from researchers in the field. Furthermore, epigenetics has contributed valuable insights to drug discovery and the identification of therapeutic targets for individuals suffering from liver fibrosis and cirrhosis. As such, this review offers a thorough discussion on the role of ncRNAs in the HSCs activation of liver fibrosis. Full article
(This article belongs to the Collection Feature Papers in Non-Coding RNA)
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23 pages, 506 KiB  
Viewpoint
Challenges in LncRNA Biology: Views and Opinions
by Donald A. Adjeroh, Xiaobo Zhou, Alexandre Rossi Paschoal, Nadya Dimitrova, Ekaterina G. Derevyanchuk, Tatiana P. Shkurat, Jeffrey A. Loeb, Ivan Martinez and Leonard Lipovich
Non-Coding RNA 2024, 10(4), 43; https://doi.org/10.3390/ncrna10040043 - 1 Aug 2024
Viewed by 1173
Abstract
This is a mini-review capturing the views and opinions of selected participants at the 2021 IEEE BIBM 3rd Annual LncRNA Workshop, held in Dubai, UAE. The views and opinions are expressed on five broad themes related to problems in lncRNA, namely, challenges in [...] Read more.
This is a mini-review capturing the views and opinions of selected participants at the 2021 IEEE BIBM 3rd Annual LncRNA Workshop, held in Dubai, UAE. The views and opinions are expressed on five broad themes related to problems in lncRNA, namely, challenges in the computational analysis of lncRNAs, lncRNAs and cancer, lncRNAs in sports, lncRNAs and COVID-19, and lncRNAs in human brain activity. 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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21 pages, 1627 KiB  
Article
High Sensitivity and Specificity Platform to Validate MicroRNA Biomarkers in Cancer and Human Diseases
by Anastassia Kanavarioti, M. Hassaan Rehman, Salma Qureshi, Aleena Rafiq and Madiha Sultan
Non-Coding RNA 2024, 10(4), 42; https://doi.org/10.3390/ncrna10040042 - 22 Jul 2024
Viewed by 1276
Abstract
We developed a technology for detecting and quantifying trace nucleic acids using a bracketing protocol designed to yield a copy number with approximately ± 20% accuracy across all concentrations. The microRNAs (miRNAs) let-7b, miR-15b, miR-21, miR-375 and miR-141 were measured in serum and [...] Read more.
We developed a technology for detecting and quantifying trace nucleic acids using a bracketing protocol designed to yield a copy number with approximately ± 20% accuracy across all concentrations. The microRNAs (miRNAs) let-7b, miR-15b, miR-21, miR-375 and miR-141 were measured in serum and urine samples from healthy subjects and patients with breast, prostate or pancreatic cancer. Detection and quantification were amplification-free and enabled using osmium-tagged probes and MinION, a nanopore array detection device. Combined serum from healthy men (Sigma-Aldrich, St. Louis, MO, USA #H6914) was used as a reference. Total RNA isolated from biospecimens using commercial kits was used as the miRNA source. The unprecedented ± 20% accuracy led to the conclusion that miRNA copy numbers must be normalized to the same RNA content, which in turn illustrates (i) independence from age, sex and ethnicity, as well as (ii) equivalence between serum and urine. miR-21, miR-375 and miR-141 copies in cancers were 1.8-fold overexpressed, exhibited zero overlap with healthy samples and had a p-value of 1.6 × 10−22, tentatively validating each miRNA as a multi-cancer biomarker. miR-15b was confirmed to be cancer-independent, whereas let-7b appeared to be a cancer biomarker for prostate and breast cancer, but not for pancreatic cancer. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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17 pages, 4066 KiB  
Article
Exploring Differentially Expressed Sperm miRNAs in Idiopathic Recurrent Pregnancy Loss and Their Association with Early Embryonic Development
by Ayushi Thapliyal, Anil Kumar Tomar, Sarla Naglot, Soniya Dhiman, Sudip Kumar Datta, Jai Bhagwan Sharma, Neeta Singh and Savita Yadav
Non-Coding RNA 2024, 10(4), 41; https://doi.org/10.3390/ncrna10040041 - 21 Jul 2024
Viewed by 1014
Abstract
The high incidence of idiopathic recurrent pregnancy loss (iRPL) may stem from the limited research on male contributory factors. Many studies suggest that sperm DNA fragmentation and oxidative stress contribute to iRPL, but their roles are still debated. MicroRNAs (miRNAs) are short non-coding [...] Read more.
The high incidence of idiopathic recurrent pregnancy loss (iRPL) may stem from the limited research on male contributory factors. Many studies suggest that sperm DNA fragmentation and oxidative stress contribute to iRPL, but their roles are still debated. MicroRNAs (miRNAs) are short non-coding RNAs that regulate various biological processes by modulating gene expression. While differential expression of specific miRNAs has been observed in women suffering from recurrent miscarriages, paternal miRNAs remain unexplored. We hypothesize that analyzing sperm miRNAs can provide crucial insights into the pathophysiology of iRPL. Therefore, this study aims to identify dysregulated miRNAs in the spermatozoa of male partners of iRPL patients. Total mRNA was extracted from sperm samples of iRPL and control groups, followed by miRNA library preparation and high-output miRNA sequencing. Subsequently, raw sequence reads were processed for differential expression analysis, target prediction, and bioinformatics analysis. Twelve differentially expressed miRNAs were identified in the iRPL group, with eight miRNAs upregulated (hsa-miR-4454, hsa-miR-142-3p, hsa-miR-145-5p, hsa-miR-1290, hsa-miR-1246, hsa-miR-7977, hsa-miR-449c-5p, and hsa-miR-92b-3p) and four downregulated (hsa-miR-29c-3p, hsa-miR-30b-5p, hsa-miR-519a-2-5p, and hsa-miR-520b-5p). Functional enrichment analysis revealed that gene targets of the upregulated miRNAs are involved in various biological processes closely associated with sperm quality and embryonic development. Full article
(This article belongs to the Section Small Non-Coding RNA)
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16 pages, 7951 KiB  
Communication
Differential Expression of lncRNAs in HIV Patients with TB and HIV-TB with Anti-Retroviral Treatment
by Victoria A. Reid, Enrique I. Ramos, Raja Veerapandian, Areanna Carmona, Shrikanth S. Gadad and Subramanian Dhandayuthapani
Non-Coding RNA 2024, 10(4), 40; https://doi.org/10.3390/ncrna10040040 - 13 Jul 2024
Viewed by 1298
Abstract
Tuberculosis (TB) is the leading cause of death among people with HIV-1 infection. To improve the diagnosis and treatment of HIV-TB patients, it is important to understand the mechanisms underlying these conditions. Here, we used an integrated genomics approach to analyze and determine [...] Read more.
Tuberculosis (TB) is the leading cause of death among people with HIV-1 infection. To improve the diagnosis and treatment of HIV-TB patients, it is important to understand the mechanisms underlying these conditions. Here, we used an integrated genomics approach to analyze and determine the lncRNAs that are dysregulated in HIV-TB patients and HIV-TB patients undergoing anti-retroviral therapy (ART) using a dataset available in the public domain. The analyses focused on the portion of the genome transcribed into non-coding transcripts, which historically have been poorly studied and received less focus. This revealed that Mtb infection in HIV prominently up-regulates the expression of long non-coding RNA (lncRNA) genes DAAM2-AS1, COL4A2-AS1, LINC00599, AC008592.1, and CLRN1-AS1 and down-regulates the expression of lncRNAs AC111000.4, AC100803.3, AC016168.2, AC245100.7, and LINC02073. It also revealed that ART down-regulates the expression of some lncRNA genes (COL4A2-AS1, AC079210.1, MFA-AS1, and LINC01993) that are highly up-regulated in HIV-TB patients. Furthermore, the interrogation of the genomic regions that are associated with regulated lncRNAs showed enrichment for biological processes linked to immune pathways in TB-infected conditions. However, intriguingly, TB patients treated with ART showed completely opposite and non-overlapping pathways. Our findings suggest that lncRNAs could be used to identify critical diagnostic, prognostic, and treatment targets for HIV-TB patients. Full article
(This article belongs to the Section Long Non-Coding RNA)
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19 pages, 5479 KiB  
Article
Expression of Transposable Elements throughout the Fasciola hepatica Trematode Life Cycle
by Elizaveta K. Skalon, Nick V. Panyushev, Olga I. Podgornaya, Anastasia R. Smolyaninova and Anna I. Solovyeva
Non-Coding RNA 2024, 10(4), 39; https://doi.org/10.3390/ncrna10040039 - 3 Jul 2024
Viewed by 1013
Abstract
Background: Transposable elements (TEs) are major components of eukaryotic genomes. The extensive body of evidence suggests that although they were once considered “genomic parasites”, transposons and their transcripts perform specific functions, such as regulation of early embryo development. Understanding the role of TEs [...] Read more.
Background: Transposable elements (TEs) are major components of eukaryotic genomes. The extensive body of evidence suggests that although they were once considered “genomic parasites”, transposons and their transcripts perform specific functions, such as regulation of early embryo development. Understanding the role of TEs in such parasites as trematodes is becoming critically important. Fasciola hepatica, a parasite affecting humans and livestock, undergoes a complex life cycle in diverse environments and hosts, and knowledge about its life cycle regulation is scarce so far. Methods: We summarized the data regarding the repetitive elements in F. hepatica and conducted bulk RNA-seq analysis across its life cycle stages. TE expression profiles were analyzed, focusing on differential expression and potential homology with previously described long non-coding RNAs (lncRNAs). Results: Differential expression analysis revealed stage-specific TE transcription patterns, notably peaking during egg and metacercariae stages. Some TEs showed homology with known lncRNAs and contained putative transcription factor binding sites. Interestingly, TE transcription levels were highest in eggs and metacercariae compared to adults, suggesting regulatory roles in trematode life cycle transitions. Conclusions: These findings suggest that TEs may play roles in regulating trematode life cycle transitions. Moreover, TE homology with lncRNAs underscores their significance in gene regulation. Full article
(This article belongs to the Section Long Non-Coding RNA)
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22 pages, 2688 KiB  
Article
Integrated Analysis of Transcriptome Profiles and lncRNA–miRNA–mRNA Competing Endogenous RNA Regulatory Network to Identify Biological Functional Effects of Genes and Pathways Associated with Johne’s Disease in Dairy Cattle
by Farzad Ghafouri, Vahid Dehghanian Reyhan, Mostafa Sadeghi, Seyed Reza Miraei-Ashtiani, John P. Kastelic, Herman W. Barkema and Masoud Shirali
Non-Coding RNA 2024, 10(4), 38; https://doi.org/10.3390/ncrna10040038 - 28 Jun 2024
Viewed by 1439
Abstract
Paratuberculosis or Johne’s disease (JD), a chronic granulomatous gastroenteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), causes huge economic losses and reduces animal welfare in dairy cattle herds worldwide. At present, molecular mechanisms and biological functions involved in immune responses to MAP infection [...] Read more.
Paratuberculosis or Johne’s disease (JD), a chronic granulomatous gastroenteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), causes huge economic losses and reduces animal welfare in dairy cattle herds worldwide. At present, molecular mechanisms and biological functions involved in immune responses to MAP infection of dairy cattle are not clearly understood. Our purpose was to integrate transcriptomic profiles and competing endogenous RNA (ceRNA) network analyses to identify key messenger RNAs (mRNAs) and regulatory RNAs involved in molecular regulation of peripheral blood mononuclear cells (PBMCs) for MAP infection in dairy cattle. In total, 28 lncRNAs, 42 miRNAs, and 370 mRNAs were identified by integrating gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In this regard, we identified 21 hub genes (CCL20, CCL5, CD40, CSF2, CXCL8, EIF2AK2, FOS, IL10, IL17A, IL1A, IL1B, IRF1, MX2, NFKB1, NFKBIA, PTGS2, SOCS3, TLR4, TNF, TNFAIP3, and VCAM1) involved in MAP infection. Furthermore, eight candidate subnets with eight lncRNAs, 29 miRNAs, and 237 mRNAs were detected through clustering analyses, whereas GO enrichment analysis of identified RNAs revealed 510, 22, and 11 significantly enriched GO terms related to MAP infection in biological process, molecular function, and cellular component categories, respectively. The main metabolic-signaling pathways related to MAP infection that were enriched included the immune system process, defense response, response to cytokine, leukocyte migration, regulation of T cell activation, defense response to bacterium, NOD-like receptor, B cell receptor, TNF, NF-kappa B, IL-17, and T cell receptor signaling pathways. Contributions of transcriptome profiles from MAP-positive and MAP-negative sample groups plus a ceRNA regulatory network underlying phenotypic differences in the intensity of pathogenicity of JD provided novel insights into molecular mechanisms associated with immune system responses to MAP infection in dairy cattle. Full article
(This article belongs to the Section Detection and Biomarkers of Non-Coding RNA)
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4 pages, 740 KiB  
Editorial
Molecular Mechanisms and Clinical Implications of Noncoding RNAs in Cancer
by Jin Wang, Xiaomeng He and Christopher Corpe
Non-Coding RNA 2024, 10(4), 37; https://doi.org/10.3390/ncrna10040037 - 25 Jun 2024
Viewed by 1464
Abstract
Noncoding RNAs (ncRNAs), which include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are RNA molecules that arise from genomic regions without protein-coding potential and display a variety of mechanisms and functions by [...] Read more.
Noncoding RNAs (ncRNAs), which include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are RNA molecules that arise from genomic regions without protein-coding potential and display a variety of mechanisms and functions by regulating gene expression at the transcriptional, RNA processing, and translational levels and participating in virtually all cellular processes [...] Full article
(This article belongs to the Special Issue Molecular Mechanisms and Clinical Implications of Non-coding RNAs in Cancer)
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