Non-Coding RNA

25 pages, 686 KB

Open AccessReview

microRNA Biomarkers in Paediatric Infection Diagnostics—Bridging the Gap Between Evidence and Clinical Application: A Scoping Review

by Oenone Rodgers, Anna De Beer and Thomas Waterfield

Non-Coding RNA 2025, 11(5), 71; https://doi.org/10.3390/ncrna11050071 - 24 Sep 2025

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Abstract

Background: Distinguishing between bacterial and viral infections in children remains a significant challenge for clinicians. Traditional biomarkers have limited utility, often leading to antibiotic overprescription due to clinician uncertainty. With rising antimicrobial resistance, novel biomarkers are needed to improve diagnosis. This scoping review [...] Read more.

Background: Distinguishing between bacterial and viral infections in children remains a significant challenge for clinicians. Traditional biomarkers have limited utility, often leading to antibiotic overprescription due to clinician uncertainty. With rising antimicrobial resistance, novel biomarkers are needed to improve diagnosis. This scoping review examines current host miRNA biomarkers for acute bacterial and viral infections in children (0–18), focusing on study methods, diagnostic metrics, and research gaps to support clinical translation. Results: Of the 1147 articles identified, 36 studies were included. Notably, 72.2% of the studies originated from Asia, and the distribution across the paediatric age groups was relatively even. A total of 17 miRNAs were validated in at least two independent studies. Three miRNAs, hsa-miR-182-5p, hsa-miR-363-3p, and hsa-miR-206, were consistently associated with bacterial infection in children. Meanwhile, nine miRNAs were associated with viral infections: hsa-miR-155, hsa-miR-29a-3p, hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-140-3p, hsa-miR-142-3p, hsa-miR-149-3p, hsa-miR-210-3p, and hsa-miR-34a-5p. Across the 12 studies reporting diagnostic accuracy metrics, miRNA biomarkers exhibited a sensitivity ranging from 70% to 100%, and a specificity ranging from 72% to 100%. The area under the curve across the studies demonstrated a range from 0.62 to 0.99. Conclusions: This scoping review highlights the potential of miRNA targets for diagnosing paediatric infections when studied rigorously. However, clinical translation is limited by poor adherence to STARD guidelines, lack of robust diagnostic metrics, and study heterogeneity. Many studies were set up with a case–control design, a design that, while highlighting differences, is more likely to identify non-specific biomarkers rather than those that are useful for novel clinical diagnostics. Full article

(This article belongs to the Section Detection and Biomarkers of Non-Coding RNA)

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24 pages, 715 KB

Open AccessReview

Role of Non-Coding RNAs in Acute Myeloid Leukemia

by Shailendra S. Maurya, Sarita Maurya and Sumit K. Chaturvedi

Non-Coding RNA 2025, 11(5), 70; https://doi.org/10.3390/ncrna11050070 - 19 Sep 2025

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Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous disease, with significantly higher incidence and fatality rates in the elderly. Even with recent decades of research progress in AML, the exact etiology of this deadly disease is still not fully understood, with recent advancements [...] Read more.

Acute myeloid leukemia (AML) is a highly heterogeneous disease, with significantly higher incidence and fatality rates in the elderly. Even with recent decades of research progress in AML, the exact etiology of this deadly disease is still not fully understood, with recent advancements in sequencing technologies highlighting the role of a growing number of non-coding RNAs (ncRNAs) that are intimately associated with AML leukemogenesis. These ncRNAs have been found to have a significant role in leukemia-related cellular processes such as cell division, proliferation, and death. A few of these non-coding RNAs exhibit potential as prognostic biomarkers. The three main groups of ncRNAs that contribute unique activities, especially in cancer, are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Their existence or altered expression levels frequently offer vital information on the diagnosis, course of treatment, and follow-up of cancer patients. The identification of ncRNAs has opened up new avenues for the diagnosis, prognosis, and therapy of acute myeloid leukemia. In order to provide a clear understanding of the significant influence that lncRNAs have on prognostic predictions and diagnostic accuracy in AML, this review aims to provide a comprehensive and insightful understanding of how these molecules actively participate in the complex landscape of the disease. Full article

(This article belongs to the Section Long Non-Coding RNA)

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16 pages, 961 KB

Open AccessReview

Long Non-Coding RNAs in Psoriasis: A Comprehensive Review of Expression Profiles, Mechanistic Insights, Genetic Associations, and Their Clinical Implications

by Judit Danis and Márta Széll

Non-Coding RNA 2025, 11(5), 69; https://doi.org/10.3390/ncrna11050069 - 19 Sep 2025

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Abstract

Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of the global population, characterized by abnormal keratinocyte proliferation and dysregulated immune responses. This review examines the emerging role of long non-coding RNAs (lncRNAs) in psoriasis pathogenesis, highlighting their significance as regulatory molecules [...] Read more.

Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of the global population, characterized by abnormal keratinocyte proliferation and dysregulated immune responses. This review examines the emerging role of long non-coding RNAs (lncRNAs) in psoriasis pathogenesis, highlighting their significance as regulatory molecules in disease initiation, progression, and chronicity. LncRNAs demonstrate distinct expression patterns in psoriatic lesions, with upregulated transcripts such as MALAT1, XIST, MIR31HG, and HOTAIR promoting keratinocyte hyperproliferation, inhibiting apoptosis, and amplifying inflammatory cascades through mechanisms including microRNA sponging and transcription factor modulation. These molecules primarily target key signaling pathways including NF-κB, STAT3, and PI3K/AKT. Conversely, downregulated lncRNAs like NEAT1, MEG3, and PRINS normally function as tumor suppressor molecules that maintain epidermal homeostasis through pro-apoptotic and anti-inflammatory mechanisms. Their reduced expression contributes to the pathological hyperproliferative phenotype characteristic of psoriatic skin. Importantly, genetic variants within lncRNA loci have been identified as significant contributors to psoriasis susceptibility and treatment responses across different populations. Single- nucleotide polymorphisms in genes such as TRAF3IP2-AS1, HOTAIR, and CDKN2B-AS1 demonstrate population-specific associations with disease risk and therapeutic outcomes, suggesting their potential utility as pharmacogenomic markers. The complex regulatory networks involving lncRNAs provide new insights into psoriasis pathogenesis and offer promising avenues for personalized treatment strategies. Integration of lncRNA profiling into clinical practice may enhance our understanding of disease heterogeneity and improve therapeutic outcomes for psoriatic patients. Full article

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25 pages, 1645 KB

Open AccessReview

Chromatin-Associated RNAs Regulate Gene Expression and Chromatin Structure

by Bingning Xie and Ann Dean

Non-Coding RNA 2025, 11(5), 68; https://doi.org/10.3390/ncrna11050068 - 12 Sep 2025

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Abstract

Inside the eukaryotic nucleus, various RNAs are associated with chromatin. These include protein-coding pre-mRNA and different types of non-coding RNAs that are referred to as chromatin-associated RNAs (caRNAs). Recent studies have revealed the important roles of these caRNAs in regulating gene expression and [...] Read more.

Inside the eukaryotic nucleus, various RNAs are associated with chromatin. These include protein-coding pre-mRNA and different types of non-coding RNAs that are referred to as chromatin-associated RNAs (caRNAs). Recent studies have revealed the important roles of these caRNAs in regulating gene expression and chromatin interactions. In this review, we discuss the recent advances in understanding caRNAs. We first focus on their mode of action, then we summarize the methods used to detect caRNAs and categorize them into three classes: RNA-centric, DNA-centric and protein-centric. Finally, we turn to the proteins that mediate their functions. Full article

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19 pages, 4115 KB

Open AccessArticle

XIST Loss Induces Variable Transcriptional Responses Dependent on Cell States

by Dongning Chen, Ikrame Naciri, Jie Wu and Sha Sun

Non-Coding RNA 2025, 11(5), 67; https://doi.org/10.3390/ncrna11050067 - 12 Sep 2025

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Abstract

Background/Objectives: The X-inactivation specific transcript (XIST) is a long noncoding RNA playing a crucial regulatory role in X chromosome inactivation (XCI)—a transcriptional regulatory process that silences one of the two X chromosomes in females to ensure proper dosage compensation between male and [...] Read more.

Background/Objectives: The X-inactivation specific transcript (XIST) is a long noncoding RNA playing a crucial regulatory role in X chromosome inactivation (XCI)—a transcriptional regulatory process that silences one of the two X chromosomes in females to ensure proper dosage compensation between male and female mammals. The transcription of XIST is maintained throughout a female’s lifespan in all somatic cells, where XIST RNA binds to the X chromosome in cis and ensures chromosome-wide gene silencing. Disrupting XIST expression can lead to transcriptional reactivation of X-linked genes and epigenetic changes affecting cell development. The prevalence of XIST regulatory effects on mammalian transcription, however, remains unclarified. Methods: Here we performed a comparative expression analysis using RNA-sequencing datasets from recently published studies and examined the consequences of XIST-deletion on transcription at the whole genome, individual chromosome, and specific gene levels. We investigated the common differentially expressed genes (DEGs) and biological pathways following XIST loss across cell types, together with differential transcriptional analysis comparing the X chromosome and autosomes using cumulative distribution fractions. We analyzed the distribution of DEGs along the X chromosome with scatterplots and correlation analysis incorporating gene density and transposable elements. Results: Our findings indicate that the loss of XIST causes transcriptional changes in the X chromosome and autosomes that differ depending on cell type and state. XIST-deletion results in differential expression of genes subject to XCI-silencing as well as genes escaping XCI. In all the cell types we analyzed, X-linked genes show differential expression across the entire X chromosome in a cluster-like pattern according to gene density and, in certain cell types, correlate strongly with short interspersed nuclear element (SINE) distributions. Conclusions: Our results demonstrate that transcriptional roles of XIST can be highly associated with cell state: stem cells have different transcriptional responses compared to differentiated cells following XIST loss. Full article

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22 pages, 3993 KB

Open AccessArticle

Cellular Delivery of Functional AntimiR Conjugated to Bio-Produced Gold Nanoparticles

by Parastoo Pourali and Veronika Benson

Non-Coding RNA 2025, 11(5), 66; https://doi.org/10.3390/ncrna11050066 - 11 Sep 2025

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Abstract

Background/Objectives: Bio-produced gold nanoparticles (AuNPs) are effective carriers of short RNAs into specialized mammalian cells. Their potential application is still limited by scarce knowledge on their uptake and intracellular fate. Gold nanoparticles that are not biologically produced (NB-AuNPs) enter specialized cells primarily [...] Read more.

Background/Objectives: Bio-produced gold nanoparticles (AuNPs) are effective carriers of short RNAs into specialized mammalian cells. Their potential application is still limited by scarce knowledge on their uptake and intracellular fate. Gold nanoparticles that are not biologically produced (NB-AuNPs) enter specialized cells primarily via clathrin-dependent endocytosis. Unlike the NB-AuNPs, the bio AuNPs possess natural surface coatings that significantly alter the AuNPs properties. Our research aimed to reveal the cellular uptake of the AuNPs with respect to delivering a functional RNA cargo. Methods: The AuNPs were conjugated with short inhibitory RNA specific to miR 135b. Mammary cancer cells 4T1 were pretreated with inhibitors of caveolin- and clathrin-mediated endocytosis and macropinocytosis. AuNPs’ uptake, fate, and miR 135b knock-down were assessed with TEM and qPCR. Results: The AuNPs-antimiR 135b conjugates entered 4T1 cells via all the tested pathways and could be seen inside the cells in early and late endosomes as well as cytoplasm. In contrast to the clathrin-dependent pathway, the caveolae-mediated endocytosis and the macropinocytosis of the AuNPs resulted in the effective targeting and reduction of the miR 135b. Conclusions: The bio-produced AuNPs can effectively enter mammalian cells simultaneously by different endocytic pathways but the delivery of functional cargo is not achieved via the clathrin-dependent endocytosis. Full article

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17 pages, 3767 KB

Open AccessArticle

Human-Specific Suppression of Hepatic Fatty Acid Catabolism by RNA-Binding Protein HuR

by Shohei Takaoka, Marcos E. Jaso-Vera and Xiangbo Ruan

Non-Coding RNA 2025, 11(5), 65; https://doi.org/10.3390/ncrna11050065 - 1 Sep 2025

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Abstract

RNA-binding proteins (RBPs) play essential roles in all major steps of RNA processing. Genetic studies in human and mouse models support that many RBPs are crucial for maintaining homeostasis in key tissues/organs, but to what extent the function of RBPs is conserved between [...] Read more.

RNA-binding proteins (RBPs) play essential roles in all major steps of RNA processing. Genetic studies in human and mouse models support that many RBPs are crucial for maintaining homeostasis in key tissues/organs, but to what extent the function of RBPs is conserved between humans and mice is not clear. Our recent study using a chimeric humanized liver mouse model found that knocking down human HuR in human hepatocytes resulted in a broad upregulation of human genes involved in fatty acid catabolism. This regulation is human-specific, as the knocking down of mouse HuR in the liver of traditional mouse models did not show these effects. To further study this human-specific role of HuR, we co-overexpressed HuR with PPARα, a master transcription factor that promotes fatty acid catabolism, in cultured cells. We found that HuR suppressed the expression of PPARα-induced fatty acid catabolism genes in human cells but not in mouse cells. We provide evidence supporting that the human-specific suppressive effect of HuR is independent of PPARα expression or location. The regulatory effects of HuR are also independent of its role in regulating mRNA stability. Using the human HMGCS2 gene as an example, we found that the suppressive effect of HuR cannot be explained by decreased promoter activity. We further provide evidence supporting that HuR suppresses the pre-mRNA processing of HMGCS2 gene, leading to accumulated intron/pre-mRNA expression of HMGCS2 gene. Furthermore, overexpression of HuR blocked and knocking down of HuR sensitized PPARα agonist-induced gene expression. By analyzing published RNA-seq data, we found compromised pre-mRNA processing for fatty acid catabolism genes in patients with fatty liver diseases, which was not observed in mouse fatty liver disease models. Our study supports the model that HuR suppresses the expression of fatty acid catabolism genes by blocking their pre-mRNA processing, which may partially explain the mild effects of PPARα agonists in treating fatty liver diseases in humans as compared with studies in mice. Full article

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43 pages, 3469 KB

Open AccessReview

Navigating the Landscape of Exosomal microRNAs: Charting Their Pivotal Role as Biomarkers in Hematological Malignancies

by Manlio Fazio, Fabio Stagno, Giuseppa Penna, Giuseppe Mirabile and Alessandro Allegra

Non-Coding RNA 2025, 11(5), 64; https://doi.org/10.3390/ncrna11050064 - 31 Aug 2025

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Abstract

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, [...] Read more.

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically, microRNAs are small non-coding RNAs, routinely detected through quantitative real-time PCR, which act as translational suppressors by regulating protein-coding genes. Considering their high stability in all body fluids and viability in circulation, research is currently focusing on this type of RNAs for the so called “liquid biopsy”, a non-invasive tool for disease diagnosis and longitudinal monitoring. However, several issues remain to be solved including the lack of standardized protocols for exosome isolation and miRNA detection. Starting with this premise, our review aims to provide a wide description of the known microRNA panels employed in the prominent hematological malignancies, which will hopefully redefine the approach to these very challenging diseases in the near future. Full article

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14 pages, 1705 KB

Open AccessArticle

Same Fragments, Different Diseases: Analysis of Identical tRNA Fragments Across Diseases Utilizing Functional and Abundance-Based Databases

by Adesupo Adetowubo, Sathyanarayanan Vaidhyanathan and Andrey Grigoriev

Non-Coding RNA 2025, 11(5), 63; https://doi.org/10.3390/ncrna11050063 - 29 Aug 2025

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Abstract

Background/Objectives: Transfer RNA-derived fragments (tRFs) are small non-coding RNAs increasingly implicated in gene regulation and disease, yet their target specificity and disease relevance remain poorly understood. This is an exploratory study that investigates the phenomenon of identical tRF sequences reported in distinct disease [...] Read more.

Background/Objectives: Transfer RNA-derived fragments (tRFs) are small non-coding RNAs increasingly implicated in gene regulation and disease, yet their target specificity and disease relevance remain poorly understood. This is an exploratory study that investigates the phenomenon of identical tRF sequences reported in distinct disease contexts and evaluates the consistency between experimental findings and predictions from both target-based and abundance-based tRF databases. Methods: Five tRFs with identical sequences across at least two peer-reviewed disease studies were selected from a recent systematic review. Their validated targets and disease associations were extracted from the literature. Motifs and predicted targets were cross-referenced using three target-oriented databases: tatDB, tRFTar, and tsRFun. In parallel, the abundance enrichment of cancer-associated tRFs was assessed in OncotRF and MINTbase using TCGA-based abundance data. Results: Among the five tRFs, only LeuAAG-001-N-3p-68-85 showed complete alignment between experimental data and both tatDB and tRFTar predictions. Most of the other four displayed at least partial overlaps in motif/binding regions with some of validated targets. tRF abundance data from MINTbase and OncotRF showed inconsistent enrichment, with only AlaAGC-002-N-3p-58-75 exhibiting concordance with its experimentally validated cancer type. Most functionally relevant tRFs were not strongly represented in abundance-only databases. Conclusions: Given the limited number of tRFs analyzed, this study serves primarily as a pilot analysis designed to generate hypotheses and guide future in-depth research, rather than offering comprehensive conclusions. We did, however, illustrate how the analysis of tRFs can benefit from utilizing currently available databases. Target-based databases more closely reflected experimental evidence for mechanistic details when a tRF or a motif match is found. Yet all database types are incomplete, including the abundance-focused tools, which often fail to capture disease-specific regulatory roles of tRFs. These findings underscore the importance of using integrated data sources for tRF annotation. As a pilot analysis, the study provides insights into how identical tRF sequences might function differently across disease contexts, highlighting areas for further investigation while pointing out the limitations of relying on expression data alone to infer functional relevance. Full article

(This article belongs to the Section Small Non-Coding RNA)

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Non-Coding RNA, Volume 11, Issue 5 (October 2025) – 9 articles

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