Journal Description
Non-Coding RNA
Non-Coding RNA
is an international, peer-reviewed, open access journal on non-coding RNA research dealing with elucidating the structure, function and biology of regulatory non-coding RNAs. Non-Coding RNA is published bimonthly online by MDPI. Cardiolinc is affiliated with Non-Coding RNA.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Genetics and Heredity) / CiteScore - Q2 (Genetics)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 21 days after submission; acceptance to publication is undertaken in 3.7 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
3.6 (2023)
Latest Articles
Circulating miRNAs in the Plasma of Post-COVID-19 Patients with Typical Recovery and Those with Long-COVID Symptoms: Regulation of Immune Response-Associated Pathways
Non-Coding RNA 2024, 10(5), 48; https://doi.org/10.3390/ncrna10050048 - 2 Sep 2024
Abstract
Following the acute phase of SARS-CoV-2 infection, certain individuals experience persistent symptoms referred to as long COVID. This study analyzed the patients categorized into three distinct groups: (1) individuals presenting rheumatological symptoms associated with long COVID, (2) patients who have successfully recovered from
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Following the acute phase of SARS-CoV-2 infection, certain individuals experience persistent symptoms referred to as long COVID. This study analyzed the patients categorized into three distinct groups: (1) individuals presenting rheumatological symptoms associated with long COVID, (2) patients who have successfully recovered from COVID-19, and (3) donors who have never contracted COVID-19. A notable decline in the expression of miR-200c-3p, miR-766-3p, and miR-142-3p was identified among patients exhibiting rheumatological symptoms of long COVID. The highest concentration of miR-142-3p was found in healthy donors. One potential way to reduce miRNA concentrations is through antibody-mediated hydrolysis. Not only can antibodies possessing RNA-hydrolyzing activity recognize the miRNA substrate specifically, but they also catalyze its hydrolysis. The analysis of the catalytic activity of plasma antibodies revealed that antibodies from patients with long COVID demonstrated lower hydrolysis activity against five fluorescently labeled oligonucleotide sequences corresponding to the Flu-miR-146b-5p, Flu-miR-766-3p, Flu-miR-4742-3p, and Flu-miR-142-3p miRNAs and increased activity against the Flu-miR-378a-3p miRNA compared to other patient groups. The changes in miRNA concentrations and antibody-mediated hydrolysis of miRNAs are assumed to have a complex regulatory mechanism that is linked to gene pathways associated with the immune system. We demonstrate that all six miRNAs under analysis are associated with a large number of signaling pathways associated with immune response-associated pathways.
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(This article belongs to the Collection Non-Coding RNAs, COVID-19, and Long-COVID)
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The Circulating miR-107 as a Potential Biomarker Up-Regulated in Castration-Resistant Prostate Cancer
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Jonathan Puente-Rivera, David Alejandro De la Rosa Pérez, Stephanie I. Nuñez Olvera, Elisa Elvira Figueroa-Angulo, José Gadú Campos Saucedo, Omar Hernández-León and María Elizbeth Alvarez-Sánchez
Non-Coding RNA 2024, 10(5), 47; https://doi.org/10.3390/ncrna10050047 - 24 Aug 2024
Abstract
Prostate cancer (PCa) is a prevalent malignancy in men globally. Current diagnostic methods like PSA testing have limitations, leading to overdiagnosis and unnecessary treatment. Castration-resistant prostate cancer (CRPC) emerges in some patients receiving androgen deprivation therapy (ADT). This study explores the potential of
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Prostate cancer (PCa) is a prevalent malignancy in men globally. Current diagnostic methods like PSA testing have limitations, leading to overdiagnosis and unnecessary treatment. Castration-resistant prostate cancer (CRPC) emerges in some patients receiving androgen deprivation therapy (ADT). This study explores the potential of circulating microRNA-107 (miR-107) in liquid biopsies as a prognosis tool to differentiate CRPC from non-castration-resistant PCa (NCRPC). We designed a case-control study to evaluate circulating miR-107 in serum as a potential prognosis biomarker. We analyzed miR-107 expression in liquid biopsies and found significantly higher levels (p < 0.005) in CRPC patients, compared to NCRPC. Notably, miR-107 expression was statistically higher in the advanced stage (clinical stage IV), compared to stages I–III. Furthermore, CRPC patients exhibited significantly higher miR-107 levels (p < 0.05), compared to NCRPC. These findings suggest that miR-107 holds promise as a non-invasive diagnostic biomarker for identifying potential CRPC patients.
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(This article belongs to the Section Detection and Biomarkers of Non-Coding RNA)
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MicroRNA Profiling as a Predictive Indicator for Time to First Treatment in Chronic Lymphocytic Leukemia: Insights from the O-CLL1 Prospective Study
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Ennio Nano, Francesco Reggiani, Adriana Agnese Amaro, Paola Monti, Monica Colombo, Nadia Bertola, Fabiana Ferrero, Franco Fais, Antonella Bruzzese, Enrica Antonia Martino, Ernesto Vigna, Noemi Puccio, Mariaelena Pistoni, Federica Torricelli, Graziella D’Arrigo, Gianluigi Greco, Giovanni Tripepi, Carlo Adornetto, Massimo Gentile, Manlio Ferrarini, Massimo Negrini, Fortunato Morabito, Antonino Neri and Giovanna Cutronaadd
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Non-Coding RNA 2024, 10(5), 46; https://doi.org/10.3390/ncrna10050046 - 23 Aug 2024
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A “watch and wait” strategy, delaying treatment until active disease manifests, is adopted for most CLL cases; however, prognostic models incorporating biomarkers have shown to be useful to predict treatment requirement. In our prospective O-CLL1 study including 224 patients, we investigated the predictive
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A “watch and wait” strategy, delaying treatment until active disease manifests, is adopted for most CLL cases; however, prognostic models incorporating biomarkers have shown to be useful to predict treatment requirement. In our prospective O-CLL1 study including 224 patients, we investigated the predictive role of 513 microRNAs (miRNAs) on time to first treatment (TTFT). In the context of this study, six well-established variables (i.e., Rai stage, beta-2-microglobulin levels, IGVH mutational status, del11q, del17p, and NOTCH1 mutations) maintained significant associations with TTFT in a basic multivariable model, collectively yielding a Harrell’s C-index of 75% and explaining 45.4% of the variance in the prediction of TTFT. Concerning miRNAs, 73 out of 513 were significantly associated with TTFT in a univariable model; of these, 16 retained an independent relationship with the outcome in a multivariable analysis. For 8 of these (i.e., miR-582-3p, miR-33a-3p, miR-516a-5p, miR-99a-5p, and miR-296-3p, miR-502-5p, miR-625-5p, and miR-29c-3p), a lower expression correlated with a shorter TTFT, whereas in the remaining eight (i.e., miR-150-5p, miR-148a-3p, miR-28-5p, miR-144-5p, miR-671-5p, miR-1-3p, miR-193a-3p, and miR-124-3p), the higher expression was associated with shorter TTFT. Integrating these miRNAs into the basic model significantly enhanced predictive accuracy, raising the Harrell’s C-index to 81.1% and the explained variation in TTFT to 63.3%. Moreover, the inclusion of the miRNA scores enhanced the integrated discrimination improvement (IDI) and the net reclassification index (NRI), underscoring the potential of miRNAs to refine CLL prognostic models and providing insights for clinical decision-making. In silico analyses on the differently expressed miRNAs revealed their potential regulatory functions of several pathways, including those involved in the therapeutic responses. To add a biological context to the clinical evidence, an miRNA–mRNA correlation analysis revealed at least one significant negative correlation between 15 of the identified miRNAs and a set of 50 artificial intelligence (AI)-selected genes, previously identified by us as relevant for TTFT prediction in the same cohort of CLL patients. In conclusion, the identification of specific miRNAs as predictors of TTFT holds promise for enhancing risk stratification in CLL to predict therapeutic needs. However, further validation studies and in-depth functional analyses are required to confirm the robustness of these observations and to facilitate their translation into meaningful clinical utility.
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Open AccessReview
Predicting the Effect of miRNA on Gene Regulation to Foster Translational Multi-Omics Research—A Review on the Role of Super-Enhancers
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Sarmistha Das and Shesh N. Rai
Non-Coding RNA 2024, 10(4), 45; https://doi.org/10.3390/ncrna10040045 - 15 Aug 2024
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
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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.
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(This article belongs to the Special Issue Perspectives and Innovations in Non-Coding RNA Bioinformatics)
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Noncoding RNA-Mediated Epigenetic Regulation in Hepatic Stellate Cells of Liver Fibrosis
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Ruoyu Gao and Jingwei Mao
Non-Coding RNA 2024, 10(4), 44; https://doi.org/10.3390/ncrna10040044 - 7 Aug 2024
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
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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.
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(This article belongs to the Collection Feature Papers in Non-Coding RNA)
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Open AccessViewpoint
Challenges in LncRNA Biology: Views and Opinions
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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
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
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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.
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(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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High Sensitivity and Specificity Platform to Validate MicroRNA Biomarkers in Cancer and Human Diseases
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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
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
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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.
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(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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Exploring Differentially Expressed Sperm miRNAs in Idiopathic Recurrent Pregnancy Loss and Their Association with Early Embryonic Development
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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
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
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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.
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(This article belongs to the Section Small Non-Coding RNA)
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Differential Expression of lncRNAs in HIV Patients with TB and HIV-TB with Anti-Retroviral Treatment
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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
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
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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.
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(This article belongs to the Section Long Non-Coding RNA)
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Open AccessArticle
Expression of Transposable Elements throughout the Fasciola hepatica Trematode Life Cycle
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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
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
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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.
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(This article belongs to the Section Long Non-Coding RNA)
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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
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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
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
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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.
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(This article belongs to the Section Detection and Biomarkers of Non-Coding RNA)
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Open AccessEditorial
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
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
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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 [...]
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(This article belongs to the Special Issue Molecular Mechanisms and Clinical Implications of Non-coding RNAs in Cancer)
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Open AccessReview
Molecular and Evolutionary Analysis of RNA–Protein Interactions in Telomerase Regulation
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Justin A. Davis and Kausik Chakrabarti
Non-Coding RNA 2024, 10(3), 36; https://doi.org/10.3390/ncrna10030036 - 18 Jun 2024
Abstract
Telomerase is an enzyme involved in the maintenance of telomeres. Telomere shortening due to the end-replication problem is a threat to the genome integrity of all eukaryotes. Telomerase inside cells depends on a myriad of protein–protein and RNA–protein interactions to properly assemble and
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Telomerase is an enzyme involved in the maintenance of telomeres. Telomere shortening due to the end-replication problem is a threat to the genome integrity of all eukaryotes. Telomerase inside cells depends on a myriad of protein–protein and RNA–protein interactions to properly assemble and regulate the function of the telomerase holoenzyme. These interactions are well studied in model eukaryotes, like humans, yeast, and the ciliated protozoan known as Tetrahymena thermophila. Emerging evidence also suggests that deep-branching eukaryotes, such as the parasitic protist Trypanosoma brucei require conserved and novel RNA-binding proteins for the assembly and function of their telomerase. In this review, we will discuss telomerase regulatory pathways in the context of telomerase-interacting proteins, with special attention paid to RNA-binding proteins. We will discuss these interactors on an evolutionary scale, from parasitic protists to humans, to provide a broader perspective on the extensive role that protein–protein and RNA–protein interactions play in regulating telomerase activity in eukaryotes.
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(This article belongs to the Collection Feature Papers in Non-Coding RNA)
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Open AccessCommunication
The miRNA Contribution in Adipocyte Maturation
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Alessandro Giammona, Simone Di Franco, Alessia Lo Dico and Giorgio Stassi
Non-Coding RNA 2024, 10(3), 35; https://doi.org/10.3390/ncrna10030035 - 12 Jun 2024
Abstract
Mesenchymal stem cells, due to their multipotent ability, are considered one of the best candidates to be used in regenerative medicine. To date, the most used source is represented by the bone marrow, despite the limited number of cells and the painful/invasive procedure
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Mesenchymal stem cells, due to their multipotent ability, are considered one of the best candidates to be used in regenerative medicine. To date, the most used source is represented by the bone marrow, despite the limited number of cells and the painful/invasive procedure for collection. Therefore, the scientific community has investigated many alternative sources for the collection of mesenchymal stem cells, with the adipose tissue representing the best option, given the abundance of mesenchymal stem cells and the easy access. Although adipose mesenchymal stem cells have recently been investigated for their multipotency, the molecular mechanisms underlying their adipogenic potential are still unclear. In this scenario, this communication is aimed at defining the role of miRNAs in adipogenic potential of adipose-derived mesenchymal stem cells via real-time PCR. Even if preliminary, our data show that cell culture conditions affect the expression of specific miRNA involved in the adipogenic potential of mesenchymal stem cells. The in vitro/in vivo validation of these results could pave the way for novel therapeutic strategies in the field of regenerative medicine. In conclusion, our research highlights how specific cell culture conditions can modulate the adipogenic potential of adipose mesenchymal stem cells through the regulation of specific miRNAs.
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(This article belongs to the Section Small Non-Coding RNA)
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Open AccessArticle
An Integrative Transcriptome Subtraction Strategy to Identify Human lncRNAs That Specifically Play a Role in Activation of Human Hepatic Stellate Cells
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Yonghe Ma, Jamie Harris, Ping Li, Chengfei Jiang, Hang Sun and Haiming Cao
Non-Coding RNA 2024, 10(3), 34; https://doi.org/10.3390/ncrna10030034 - 6 Jun 2024
Abstract
Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from “activated” hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to
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Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from “activated” hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to define the role of human long non-coding RNAs (lncRNAs) in hHSC activation. To address this challenge, we identified another cell type that acts via a diverse gene network to promote fibrogenesis. Then, we identified the lncRNAs that were differentially regulated in activated hHSCs and the other profibrotic cell. Next, we conducted concurrent analysis to identify those lncRNAs that were specifically involved in fibrogenesis. We tested and confirmed that transdifferentiation of vascular smooth muscle cells (VSMCs) represents such a process. By overlapping TGFβ-regulated lncRNAs in multiple sets of hHSCs and VSMCs, we identified a highly selected list of lncRNA candidates that could specifically play a role in hHSC activation. We experimentally characterized one human lncRNA, named CARMN, which was significantly regulated by TGFβ in all conditions above. CARMN knockdown significantly reduced the expression levels of a panel of marker genes for hHSC activation, as well as the levels of ECM deposition and hHSC migration. Conversely, gain of function of CARMN using CRISPR activation (CRISPR-a) yielded the completely opposite effects. Taken together, our work addresses a bottleneck in identifying human lncRNAs that specifically play a role in hHSC activation and provides a framework to effectively select human lncRNAs with significant pathophysiological role.
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(This article belongs to the Special Issue Roles of Non-coding RNAs in Drug Metabolism and Disposition)
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Open AccessArticle
Investigation of Antihypertensive Properties of Chios Mastic via Monitoring microRNA-21 Expression Levels in the Plasma of Well-Controlled Hypertensive Patients
by
Maria Tsota, Panagiota Giardoglou, Evangelia Mentsiou-Nikolaou, Panagiotis Symianakis, Ioanna Panagiota Kalafati, Anastasia-Areti Kyriazopoulou-Korovesi, Lasthenis Angelidakis, Maria Papaioannou, Christina Konstantaki, HYPER-MASTIC Consortium, Kimon Stamatelopoulos and George V. Dedoussis
Non-Coding RNA 2024, 10(3), 33; https://doi.org/10.3390/ncrna10030033 - 31 May 2024
Abstract
Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds
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Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds which modify microRNAs’ (small, expression-regulating molecules) expression. In this study, we investigated the antihypertensive properties of Chios mastic through the assessment of miR-21 levels. Herein, plasma samples of 57 individuals with hypertension, recruited for the purposes of the HYPER-MASTIC study, were analyzed. This was a clinical trial with Chios mastic supplements in which the patients were divided into groups receiving high and low mastic doses and placebo supplements, respectively. miR-21 was significantly upregulated in patients compared to normotensive individuals. Mean changes in miR-21 levels were statistically significant, after adjusting for sex and age, between the placebo and low-dose group and between the low- and high-dose group. Post-intervention miR-21 levels were positively associated with night-time systolic blood pressure, pulse pressure, and central systolic mean arterial pressure and negatively associated with night-time pulse wave velocity in the low-dose group. Our findings suggest a potential implication of miR-21 in the association of Chios mastic with night-time blood pressure measurements.
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(This article belongs to the Topic MicroRNA: Mechanisms of Action, Physio-Pathological Implications, and Disease Biomarkers, 2nd Volume)
(This article belongs to the Section Detection and Biomarkers of Non-Coding RNA)
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Open AccessArticle
MEF2C Directly Interacts with Pre-miRNAs and Distinct RNPs to Post-Transcriptionally Regulate miR-23a-miR-27a-miR-24-2 microRNA Cluster Member Expression
by
Estefanía Lozano-Velasco, Carlos Garcia-Padilla, Miguel Carmona-Garcia, Alba Gonzalez-Diaz, Angela Arequipa-Rendon, Amelia E. Aranega and Diego Franco
Non-Coding RNA 2024, 10(3), 32; https://doi.org/10.3390/ncrna10030032 - 17 May 2024
Abstract
Transcriptional regulation constitutes a key step in gene expression regulation. Myocyte enhancer factor 2C (MEF2C) is a transcription factor of the MADS box family involved in the early development of several cell types, including muscle cells. Over the last decade, a novel layer
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Transcriptional regulation constitutes a key step in gene expression regulation. Myocyte enhancer factor 2C (MEF2C) is a transcription factor of the MADS box family involved in the early development of several cell types, including muscle cells. Over the last decade, a novel layer of complexity modulating gene regulation has emerged as non-coding RNAs have been identified, impacting both transcriptional and post-transcriptional regulation. microRNAs represent the most studied and abundantly expressed subtype of small non-coding RNAs, and their functional roles have been widely documented. On the other hand, our knowledge of the transcriptional and post-transcriptional regulatory mechanisms that drive microRNA expression is still incipient. We recently demonstrated that MEF2C is able to transactivate the long, but not short, regulatory element upstream of the miR-23a-miR-27a-miR-24-2 transcriptional start site. However, MEF2C over-expression and silencing, respectively, displayed distinct effects on each of the miR-23a-miR-27a-miR-24-2 mature cluster members without affecting pri-miRNA expression levels, thus supporting additional MEF2C-driven regulatory mechanisms. Within this study, we demonstrated a complex post-transcriptional regulatory mechanism directed by MEF2C in the regulation of miR-23a-miR-27a-miR-24-2 cluster members, distinctly involving different domains of the MEF2C transcription factor and the physical interaction with pre-miRNAs and Ksrp, HnRNPa3 and Ddx17 transcripts.
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(This article belongs to the Section Small Non-Coding RNA)
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Open AccessArticle
The RNAi Machinery in the Fungus Fusarium fujikuroi Is Not Very Active in Synthetic Medium and Is Related to Transposable Elements
by
Javier Pardo-Medina, Tim A. Dahlmann, Minou Nowrousian, M. Carmen Limón and Javier Avalos
Non-Coding RNA 2024, 10(3), 31; https://doi.org/10.3390/ncrna10030031 - 16 May 2024
Abstract
Small RNAS (sRNAs) participate in regulatory RNA interference (RNAi) mechanisms in a wide range of eukaryotic organisms, including fungi. The fungus Fusarium fujikuroi, a model for the study of secondary metabolism, contains a complete set of genes for RNAi pathways. We have
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Small RNAS (sRNAs) participate in regulatory RNA interference (RNAi) mechanisms in a wide range of eukaryotic organisms, including fungi. The fungus Fusarium fujikuroi, a model for the study of secondary metabolism, contains a complete set of genes for RNAi pathways. We have analyzed by high-throughput sequencing the content of sRNAs in total RNA samples of F. fujikuroi grown in synthetic medium in the dark or after 1 h of illumination, using libraries below 150 nt, covering sRNAs and their precursors. For comparison, a parallel analysis with Fusarium oxysporum was carried out. The sRNA reads showed a higher proportion of 5′ uracil in the RNA samples of the expected sizes in both species, indicating the occurrence of genuine sRNAs, and putative miRNA-like sRNAs (milRNAS) were identified with prediction software. F. fujikuroi carries at least one transcriptionally expressed Ty1/copia-like retrotransposable element, in which sRNAs were found in both sense and antisense DNA strands, while in F. oxysporum skippy-like elements also show sRNA formation. The finding of sRNA in these mobile elements indicates an active sRNA-based RNAi pathway. Targeted deletion of dcl2, the only F. fujikuroi Dicer gene with significant expression under the conditions tested, did not produce appreciable phenotypic or transcriptomic alterations.
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(This article belongs to the Section Small Non-Coding RNA)
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Open AccessSystematic Review
A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases
by
Gantsetseg Garmaa, Stefania Bunduc, Tamás Kói, Péter Hegyi, Dezső Csupor, Dariimaa Ganbat, Fanni Dembrovszky, Fanni Adél Meznerics, Ailar Nasirzadeh, Cristina Barbagallo and Gábor Kökény
Non-Coding RNA 2024, 10(3), 30; https://doi.org/10.3390/ncrna10030030 - 3 May 2024
Cited by 3
Abstract
Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and
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Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and murine CKDs. Comprehensive literature searches were conducted on five databases. Subgroup analyses of kidney diseases, sample types, disease stages, and species were conducted. A total of 38 human and 12 murine eligible studies were analyzed using Robust Rank Aggregation (RRA) and vote-counting analyses. Gene set enrichment analyses of miRNA signatures in each kidney disease were conducted using DIANA-miRPath v4.0 and MIENTURNET. As a result, top target genes, Gene Ontology terms, the interaction network between miRNA and target genes, and molecular pathways in each kidney disease were identified. According to vote-counting analysis, 145 miRNAs were dysregulated in human kidney diseases, and 32 were dysregulated in murine CKD models. By RRA, miR-26a-5p was significantly reduced in the kidney tissue of Lupus nephritis (LN), while miR-107 was decreased in LN patients’ blood samples. In both species, epithelial-mesenchymal transition, Notch, mTOR signaling, apoptosis, G2/M checkpoint, and hypoxia were the most enriched pathways. These miRNA signatures and their target genes must be validated in large patient cohort studies.
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(This article belongs to the Topic MicroRNA: Mechanisms of Action, Physio-Pathological Implications, and Disease Biomarkers, 2nd Volume)
(This article belongs to the Section Small Non-Coding RNA)
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(This article belongs to the Section Small Non-Coding RNA)
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Open AccessArticle
Dysregulation of a Subset of Circulating and Vesicle-Associated miRNA in Pancreatic Cancer
by
Giulia Girolimetti, Iulia Andreea Pelisenco, Leonardo Henry Eusebi, Claudio Ricci, Beatrice Cavina, Ivana Kurelac, Tiziano Verri, Matteo Calcagnile, Pietro Alifano, Alessandro Salvi, Cecilia Bucci and Flora Guerra
Non-Coding RNA 2024, 10(3), 29; https://doi.org/10.3390/ncrna10030029 - 1 May 2024
Cited by 3
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasia, characterized by early metastasis, low diagnostic rates at early stages, resistance to drugs, and poor prognosis. There is an urgent need to better characterize this disease in order to identify efficient diagnostic/prognostic
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasia, characterized by early metastasis, low diagnostic rates at early stages, resistance to drugs, and poor prognosis. There is an urgent need to better characterize this disease in order to identify efficient diagnostic/prognostic biomarkers. Since microRNAs (miRNAs) contribute to oncogenesis and metastasis formation in PDAC, they are considered potential candidates for fulfilling this task. In this work, the levels of two miRNA subsets (involved in chemoresistance or with oncogenic/tumor suppressing functions) were investigated in a panel of PDAC cell lines and liquid biopsies of a small cohort of patients. We used RT-qPCR and droplet digital PCR (ddPCR) to measure the amounts of cellular- and vesicle-associated, and circulating miRNAs. We found that both PDAC cell lines, also after gemcitabine treatment, and patients showed low amounts of cellular-and vesicle-associated miR-155-5p, compared to controls. Interestingly, we did not find any differences when we analyzed circulating miR-155-5p. Furthermore, vesicle-related miR-27a-3p increased in cancer patients compared to the controls, while circulating let-7a-5p, miR-221-3p, miR-23b-3p and miR-193a-3p presented as dysregulated in patients compared to healthy individuals. Our results highlight the potential clinical significance of these analyzed miRNAs as non-invasive diagnostic molecular tools to characterize PDAC.
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(This article belongs to the Special Issue Extracellular Vesicles and ncRNA)
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