Search Results (279)

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and play important roles in plant development and reproduction. Liriodendron chinense, a representative woody species of Magnoliaceae, produces a large quantity of pollen but exhibits low natural seed set. Despite numerous studies on factors influencing its low seed production, the molecular mechanisms underlying this reproductive limitation remain poorly understood. Here, we performed small RNA sequencing and transcriptome analyses across five tissues of L. chinense, including leaf, calyx, petal, pistil, and pollen. Genome-wide identification yielded 688 miRNAs, comprising both conserved and species-specific members. Expression-based clustering revealed that miRNAs are organized into distinct, tissue-associated modules rather than being uniformly expressed across organs. Among these, a pollen-enriched miRNA module was clearly separated from those associated with leaves and other floral tissues. By integrating sRNA-seq and RNA-seq data, we identified miRNA–target pairs displaying anticorrelated expression patterns, providing expression-level support for miRNA mediated regulation. In pollen, two complementary regulatory modes were observed: low-abundance miRNAs associated with highly expressed target genes, and highly expressed miRNAs associated with repressed targets. The predicted targets of pollen-associated miRNAs were enriched in biological processes central to pollen development, including signal transduction, polarity establishment, vesicle trafficking, and cell wall biogenesis. Overall, this study provides a comprehensive, tissue-resolved view of miRNA expression and pollen-associated miRNA–target relationships in L. chinense, offering candidate regulatory modules for future functional studies of pollen development. Full article

COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is clinically defined by persistent symptoms that endure beyond acute infection and affect multiple organ systems, including the immune, cardiopulmonary, neurological, and metabolic axes. The underlying mechanisms remain poorly resolved, limiting the development of targeted diagnostics and therapeutics. MicroRNAs (miRNAs), as key post-transcriptional regulators of gene expression, control inflammatory networks, antiviral responses, mitochondrial bioenergetics, and fibrotic pathways, all of which are implicated in long COVID pathogenesis. Recent studies show durable changes in circulating miRNA signatures months after recovery from the acute phase, suggesting a role in maintaining chronic immune activation and metabolic dysfunction. Importantly, circulating miRNAs are stable, quantifiable in biofluids, and reflect systems-level dysregulation, positioning them as promising biomarker candidates for patient stratification, symptom clustering, and disease monitoring. Moreover, miRNA-directed interventions, such as mimics and antagomiRs, represent an emerging precision-medicine strategy to correct sustained molecular disturbances. This review summarizes current evidence linking miRNAs to long COVID, highlights their biomarker potential, and discusses therapeutic avenues that may help advance mechanism-based interventions for this globally emerging chronic condition. Full article

Background: Diagnostic discrimination between ischemic stroke (IS) and hemorrhagic stroke (HS) is required for successful intervention with time-critical acute treatments. The available data on blood-based RNA biomarkers and discrimination between IS and HS are limited. This systematic review aimed to examine and summarize the existing literature on potentially useful blood-based RNA biomarkers that may aid in preclinical acute diagnosis. Methods: We systematically reviewed the literature on the ability of blood-based RNA biomarkers to discriminate between IS and HS according to PRISMA guidelines. We searched PubMed, EMBASE, The Cochrane Library, and The Web of Science for eligible randomized controlled trials, observational studies, and case–control studies published in the English language without time limitation. The risk of bias was evaluated using the Newcastle–Ottawa Scale. Results: We included eight studies with a total of 728 patients (436 with IS and 292 with HS) in our review. The study quality was good in five and fair in three investigations. No meta-analysis was performed due to high heterogeneity in methods and study endpoints. Reported biomarkers include miRNA-124-3p, miRNA-16, miRNA-340-5p, lncRNA XIST (X-inactive specific transcript), PFKFB3 mRNA (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase), tRNA derivatives, tRNA fragments, extracellular miRNAs, transcriptome changes, and MCEMP1 gene expression. Assessment techniques varied widely across studies, ranging from RNA sequencing to qPCR, microarray, human transcriptome array, and ELISA. MicroRNA-124-3p, miRNA-340-5p, lncRNA XIST, PFKFB3 mRNA, and MCEMP1 gene expression differed significantly between IS and HS. In one study, principal component analysis and unsupervised learning demonstrated the utility of hierarchical clustering of differentially expressed exons to discriminate between HS and IS. Conclusions: This review demonstrates the utility of single RNA-based targets and clusters that may have diagnostic value in distinguishing IS from HS. However, the current body of evidence is limited by considerable methodological heterogeneity between studies. Registration: This systematic review was prospectively registered on PROSPERO on 21 April 2023 (CRD42023411203). Full article

Background: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition influenced by both genetic and non-genetic factors, although the underlying pathomechanisms remain unclear. We systematically analyzed microRNA (miRNA) expression and associated functional pathways in ASD to evaluate their potential as prenatal/postnatal, diagnostic, and prognostic biomarkers. Methods: Peripheral blood mononuclear cells from 12 Sicilian patients with ASD (eight with normal cognitive function) and 15 healthy controls were analyzed using small RNA sequencing. Differential expression analysis was performed with DESeq2 (|fold change| ≥ 1.5; adjusted p ≤ 0.05). Functional enrichment and network analyses were conducted using Ingenuity Pathway Analysis, focusing on Diseases and Biofunctions. Results: 998 miRNAs were differentially expressed in ASD, 424 upregulated and 553 downregulated. Enriched pathways were primarily associated with psychological and neurological disorders. Network analysis highlighted three principal interaction clusters related to inflammation, cell survival and mechanotransduction, synaptic plasticity, and neuronal excitability. Four miRNAs (miR-296-3p, miR-27a, miR-146a-5p, and miR-29b-3p) emerged as key regulatory candidates. Conclusions: The marked divergence in miRNA expression between ASD and controls suggests distinct regulatory patterns, thus reinforcing the central involvement of inflammatory, autoimmune, and infectious mechanisms in ASD, mediated by miRNAs regulating S100 family genes, neuronal migration, and synaptic communication. However, rather than defining a predictive biomarker panel, this study identified candidate miRNAs and regulatory networks that may be relevant to ASD pathophysiology. As such, further validation in appropriately powered cohorts with predictive modeling frameworks are warranted before any biomarker or diagnostic implications can be inferred. Full article

Nonsteroidal anti-inflammatory drugs (NSAIDs) can exacerbate urticaria and/or angioedema in up to 30% of patients with chronic urticaria (CU), representing a distinct subtype characterized by heightened inflammation and leukotriene-driven pathophysiology. MicroRNAs (miRNAs) are post-transcriptional regulators that modulate immune and inflammatory responses. This study aimed to identify differentially expressed miRNAs (DEMs) according to NSAID hypersensitivity status and to elucidate their molecular networks in CU. Serum miRNA profiles were analyzed in 14 NSAID-exacerbated CU (NECU) and 16 NSAID-tolerant CU (NTCU) patients using an Affymetrix GeneChip^® miRNA 4.0 Array. DEMs were identified (fold difference > 1.5, p < 0.05), and validated targets were retrieved from the multiMiR database for network construction and Gene Ontology enrichment analyses. NECU patients exhibited a higher frequency of angioedema and systemic corticosteroid use than NTCU patients. Eight DEMs were identified, including upregulated miR-5001-5p, miR-4270, and miR-6869-5p, and downregulated miR-6511b-5p, miR-2277-5p, and miR-378h in NECU. Network integration revealed AGO2-BTG2-LMNB2, NFIC-ZZZ3, and NUFIP2-GLG1 as central clusters, implicating dysregulation of mRNA decay and inflammatory signaling pathways. Reduced miR-6511b-5p expression may derepress BRG1, enhancing chromatin accessibility for inflammatory and leukotriene-synthetic genes. Distinct miRNA signatures differentiate NECU from NTCU, implying a miR-5001-5p/miR-6511b-5p–mRNA decay axis that links impaired post-transcriptional regulation with leukotriene-driven inflammation in CU. These findings highlight candidate miRNAs as potential biomarkers for disease endotyping and therapeutic stratification. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a highly prevalent hepatic condition closely linked to metabolic syndrome (MetS). Epigenetic regulators such as microRNAs (miRNAs) have emerged as critical modulators of the molecular pathways underlying MASLD pathogenesis, offering new perspectives for non-invasive diagnosis and targeted therapy. This study aimed to identify and characterize target genes and pathways regulated by two key hepatic miRNAs, namely miR-122 and miR-29a, through a comprehensive in silico bioinformatics approach, to better understand their functional roles in MASLD and MetS. Methods: Target genes of miR-122 and miR-29a were predicted using three databases (TargetScan, DIANA-microT-CDS, and miRWalk), and those identified by at least two databases were selected for downstream analyses. Functional enrichment was performed using Gene Ontology and KEGG pathway analysis. Gene networks and biological process maps were constructed using Metascape, clusterProfiler and Cytoscape. Results: miR-122 was found to negatively regulate genes involved in lipid metabolism, insulin signaling, and inflammatory pathways, including PPARGC1A, PPARA, LPL, TLR4, and HMGCR, contributing to insulin resistance and liver dysfunction. By contrast, miR-29a demonstrated potential hepatoprotective effects by targeting LEP, INSR, IL13, and IL18, enhancing insulin sensitivity and reducing fibrogenic activity. Enrichment analysis revealed strong associations with biological processes, such as STAT phosphorylation, lipid homeostasis, and inflammatory signaling, as well as associations with cellular components, including lipoproteins and plasma membranes. miR-122 and miR-29a exhibit opposing regulatory functions in MASLD pathogenesis. Whereas miR-122 is associated with disease progression, miR-29a acts protectively. These miRNAs may serve as promising biomarkers and therapeutic targets in MASLD and related metabolic conditions. Further validation through experimental and clinical studies is warranted. Full article

Diffuse large B-cell lymphoma (DLBCL) is the most common and clinically aggressive subtype of non-Hodgkin lymphoma (NHL). While novel therapies such as rituximab and polatuzumab vedotin have led to improved outcomes, approximately 35% of patients eventually develop relapsed or refractory disease. MicroRNAs (miRNAs), a class of endogenous single-stranded RNAs approximately 22 nucleotides in length, play a pivotal role in the regulation of gene expression at the post-transcriptional level through interactions with complementary target RNAs and contribute significantly to the development, progression, and treatment response of DLBCL. Oncogenic miRNAs, such as miR-155, miR-21, and the miR-17–92 cluster, promote proliferation, survival, immune evasion, and therapy resistance by modulating pathways including PI3K/AKT, NF-κB, and MYC. Conversely, tumor-suppressive miRNAs such as miR-34a, miR-144, miR-181a, and miR-124-3p inhibit oncogene activity and enhance apoptosis, with their loss often associated with adverse outcomes. Among these, miR-155 and miR-21 are particularly well studied, playing central roles in both tumor progression and remodeling of the tumor microenvironment. This review summarizes current evidence on the biological and clinical relevance of miRNAs in DLBCL, emphasizing their diagnostic and prognostic potential. Full article

Early fruit development in tomato is driven by complex gene expression patterns and metabolic reprogramming, a crucial phase that shapes the fruit’s final size and structure. Previous studies using the Micro-Tom model have largely focused on later stages of development, especially ripening, leaving early developmental processes relatively unexplored. To address this knowledge gap, we performed RNA-seq analyses on Micro-Tom fruits harvested at three key developmental stages: 3, 5, and 8 days post-anthesis (DPA). Pairwise differential gene expression analyses revealed that the most extensive transcriptional reprogramming occurs during the transition from 5 to 8 DPA, while comparatively fewer changes were observed between 3 and 5 DPA. K-means clustering of 11,035 stably expressed genes revealed nine distinct expression profiles associated with specific developmental phases, including cell proliferation, transition, and cell expansion. Integrating transcriptomic and metabolomic datasets uncovered coordinated shifts in gene expression and metabolite accumulation, highlighting both conserved regulatory mechanisms and cultivar-specific pathways governing early fruit development. These findings advance our understanding of the molecular regulation of early fruit development in Micro-Tom tomatoes and provide a basis for future efforts to improve fruit quality and yield. Full article

Climate change increasingly challenges viticulture, demanding innovative and sustainable strategies to preserve grapevine productivity and grape quality. MicroRNA-encoded peptides (miPEPs) have emerged as natural regulators of gene expression, providing a novel mechanism for fine-tuning plant metabolism. Here, we evaluated whether exogenous application of miPEP164c, previously shown to repress VviMYBPA1 in vitro, can modulate flavonoid pathways in field-grown grapevines (Vitis vinifera L. cv. Vinhão). Grape clusters were sprayed with 1 µM miPEP164c before and during véraison, and molecular, biochemical, and metabolomic analyses were performed at harvest. miPEP164c treatment significantly upregulated pre-miR164c transcripts, leading to post-transcriptional silencing of VviMYBPA1 and strong downregulation of the proanthocyanidin-related genes VviLAR1, VviLAR2, and VviANR. Correspondingly, LAR and ANR activities were reduced by up to 75%, and total proanthocyanidin content decreased by nearly 30%. Metabolomic profiling showed reduced flavan-3-ols and moderate shifts in phenolic acids and stilbenoids, while anthocyanins increased slightly. Overall, miPEP164c reprogrammed flavonoid metabolism under vineyard conditions, selectively lowering tannin biosynthesis without affecting other key phenolics. These findings establish miPEPs as promising biostimulants for precise modulation of grape berry composition, offering new tools for urgently needed sustainable and precision viticulture and improved wine quality under climate change and the increasing environmental challenges it poses. Full article

This article aims to point out new perspectives opened by genomics and epigenomics in skin rejuvenation strategies which target the main hallmarks of the ageing. In this respect, this article presents a concise overview on: the clinical relevance of the most important clocks and biomarkers used in skin anti-ageing strategy evaluation, the fundamentals, the main illustrating examples preclinically and clinically tested, the critical insights on knowledge gaps and future research perspectives concerning the most relevant skin anti-ageing and rejuvenation strategies based on novel epigenomic and genomic acquisitions. Thus the review dedicates distinct sections to: senolytics and senomorphics targeting senescent skin cells and their senescent-associated phenotype; strategies targeting genomic instability and telomere attrition by stimulation of the deoxyribonucleic acid (DNA) repair enzymes and proteins essential for telomeres’ recovery and stability; regenerative medicine based on mesenchymal stem cells or cell-free products in order to restore skin-resided stem cells; genetically and chemically induced skin epigenetic partial reprogramming by using transcription factors or epigenetic small molecule agents, respectively; small molecule modulators of DNA methylases, histone deacetylases, telomerases, DNA repair enzymes or of sirtuins; modulators of micro ribonucleic acid (miRNA) and long-non-coding ribonucleic acid (HOTAIR’s modulators) assisted or not by CRISPR-gene editing technology (CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats); modulators of the most relevant altered nutrient-sensing pathways in skin ageing; as well as antioxidants and nanozymes to address mitochondrial dysfunctions and oxidative stress. In addition, some approaches targeting skin inflammageing, altered skin proteostasis, (macro)autophagy and intercellular connections, or skin microbiome, are very briefly discussed. The review also offers a comparative analysis among the newer genomic/epigenomic-based skin anti-ageing strategies vs. classical skin rejuvenation treatments from various perspectives: efficacy, safety, mechanism of action, evidence level in preclinical and clinical data and regulatory status, price range, current limitations. In these regards, a concise overview on senolytic/senomorphic agents, topical nutrigenomic pathways’ modulators and DNA repair enzymes, epigenetic small molecules agents, microRNAs and HOTAIRS’s modulators, is illustrated in comparison to classical approaches such as tretinoin and peptide-based cosmeceuticals, topical serum with growth factors, intense pulsed light, laser and microneedling combinations, chemical peels, botulinum toxin injections, dermal fillers. Finally, the review emphasizes the future research directions in order to accelerate the clinical translation of the (epi)genomic-advanced knowledge towards personalization of the skin anti-ageing strategies by integration of individual genomic and epigenomic profiles to customize/tailor skin rejuvenation therapies. Full article

The rapid advancements in high-throughput technologies have led to a dramatic increase in diverse -omics data types, enabling comprehensive analyses, especially for complex diseases like cancer. Despite the development of multi-omics approaches, the challenges of scaling integration to massive, heterogeneous -omics datasets suggest that novel computational tools need to be designed. In this study, we propose an approach for integrating microRNA (miRNA) and messenger RNA (mRNA) expression data, incorporating prior biological knowledge (PBK). This approach scores and ranks groups of miRNAs and their associated genes using cross-validation iterations. The proposed method incorporates a Pattern detection (P) component to identify molecular motifs unique to each biological group. The analysis also facilitates the visualization of the groups, facilitating the identification of co-occurring groups and their characteristic features across iterations. Furthermore, the groups are scored using an over-representation analysis through a new Enrichment (E) component in each iteration. The clusters of the groups based on the Enrichment Scores (ESs) are visualized in a heatmap to obtain novel insights into the collective behavior and dependencies of the groups, aiming to understand the molecular mechanisms of complex diseases. The developed G-S-M-E tool not only provides performance metrics and biological scores at the group level but also offers comprehensive insights into intricate multi-omics interactions. In summary, our study emphasizes the importance of mathematical and data science methodologies in elucidating intricate multi-omics integration, yielding a formalized approach that deepens our comprehension of complex diseases. Full article

The FAM171A2 gene encodes a transmembrane protein that is not well characterized but is implicated in signaling, vesicle trafficking, and interactions with the extracellular matrix. Its specific role in gynecologic malignancies has yet to be defined. To our knowledge, this is the first systematic study to comprehensively assess FAM171A2 expression, clinical relevance, and molecular network interactions in gynecologic malignancies. We employed an integrative approach utilizing multi-platform transcriptomic and proteomic resources—GEPIA2, TNMplot, TIMER2, UALCAN, KM-plotter, Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), STRING, TargetScan, and ENCORI—to comprehensively profile FAM171A2 expression, its clinicopathologic correlations, survival associations, predicted interaction networks, and post-transcriptional regulation in ovarian cancer (OV) and uterine corpus endometrial carcinoma (UCEC). Immunohistochemical analysis from the HPA indicated low or undetectable levels of the FAM171A2 protein in OV and UCEC. In contrast, RNA sequencing analyses demonstrated upregulated mRNA expression in OV and a modest, non-significant increase in UCEC compared to normal tissues. Pan-cancer screening using TNMplot and TIMER2 revealed elevated expression in gynecologic tumors relative to most other cancer types. In OV, UALCAN analysis identified associations with demographic and molecular characteristics, such as increased expression in TP53-mutant tumors, while trends related to stage and grade were minimal. Similarly, stratifications in UCEC suggested modulation by race, body mass index (BMI), and menopausal status rather than stage. Survival analyses using KM-plotter showed no significant association with overall survival in either type of cancer. TargetScan predicted 211 microRNAs potentially targeting FAM171A2, and ENCORI correlations supported tumor-type-specific post-transcriptional regulation: in OV, negative correlations were observed with miR-15b-5p, miR-16-5p, and miR-497-5p, along with long non-coding RNA (lncRNA) effects, including positive correlations with BACE1-AS and negative correlations with PVT1 and UCA1. In UCEC, significant negative correlations were found with LINC00582, LINC-ROR, MEG3, NEAT1, and SNHG12. STRING network analysis suggested two modules associated with FAM171A2: a neuronal/synaptic cluster, exemplified by NPTX1, and an immune/transcriptional cluster, exemplified by ZNF696. Validation using the GEO showed mixed results: two UCEC datasets were non-significant, whereas one OV cohort (GSE36368) exhibited higher tumor expression. FAM171A2 demonstrates context-dependent expressions that are modulated post-transcriptionally in gynecologic cancers. While it is not independently prognostic, it may serve as a molecular hub at the intersection of neuronal and immune pathways, warranting further mechanistic investigations and exploration as a panel-based biomarker. Full article

Uterine leiomyosarcoma (uLMS) is a rare, highly aggressive malignancy of uterine smooth muscle, associated with early metastasis, frequent recurrence, and poor prognosis. Accurate preoperative diagnosis remains difficult given that clinical and radiologic features often overlap with benign leiomyomas, and no reliable biomarkers are currently available. This review summarizes recent evidence on the role of microRNAs (miRNAs) in the biology and clinical management of uLMS. Literature from molecular and translational studies was examined to identify dysregulated miRNAs, their target pathways, and potential diagnostic and therapeutic applications. uLMS displays a characteristic miRNA profile, including downregulation of tumor-suppressive miRNAs such as the miR-29 and miR-200 families and upregulation of oncogenic miRNAs including miR-21 and the miR-183~96~182 cluster, leading to activation of PI3K/AKT/mTOR signaling and epithelial–mesenchymal transition (EMT). Circulating and tissue miRNAs show promise as minimally invasive biomarkers for differentiating uLMS from leiomyomas, predicting prognosis, and guiding therapy. Emerging therapeutic approaches aim to restore the tumor-suppressive miRNAs or inhibit oncogenic ones using mimics or antagomiRs. Overall miRNAs represent critical regulators of uLMS pathogenesis and hold significant potential for precision diagnosis, prognostication, and targeted therapy, though larger validation studies and improved delivery systems are required before clinical translation. Full article

Background: MicroRNA-133 (miR-133) has been implicated in diverse cancers as a tumor suppressor, yet the isoform-specific contributions of miR-133A1, miR-133A2, and miR-133B in colorectal cancer (CRC) remain unclear. Methods: We established stable colorectal cancer cell lines expressing each miR-133 isoform and performed isoform-level transcriptomic profiling. Differentially expressed genes (DEGs) were identified relative to parental cells and subjected to gene ontology (GO) and KEGG enrichment analyses. Comparative analyses highlighted both shared and distinct biological pathways regulated by each isoform. Results: Venn diagram and clustering analyses revealed that all three isoforms shared a core regulatory program, with 34 genes consistently upregulated and 195 genes downregulated across all isoforms, while also displaying isoform-specific DEGs. miR-133A1, miR-133A2, and miR-133B showed predominantly convergent transcriptional programs, with subtle quantitative differences observed primarily in KI133B. Heatmap analysis of representative genes confirmed both overlapping and isoform-specific expression changes, with survival- and proliferation-associated genes more strongly upregulated in miR-133A2 and miR-133B. Conclusion: These findings suggest that miR-133 isoforms exert both shared and subtly divergent regulatory functions in colorectal cancer, coordinating apoptosis, proliferation, migration, and signaling network modulation. Isoform-specific transcriptional regulation of miR-133 may contribute to tumor progression and represents a potential biomarker and therapeutic target in CRC. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is one of the world’s deadliest cancers; however, the mechanisms that contribute to its aggressiveness are poorly understood. In the recent literature, overexpression of the Chromosome 19 MicroRNA Cluster (C19MC) has been associated with an aggressive phenotype and unfavorable prognosis in HCC. However, the molecular consequences of C19MC overexpression in HCC remain poorly understood. Methods: Here, we created a constitutive C19MC-overexpressing HCC model and used two different CRISPR-engineered C19MC-overexpressing HCC models to analyze phenotype and transcriptomic changes. Results: We observed that C19MC overexpression induces cancer stem cell (CSC) phenotypic features in vitro and analyzed transcriptomic changes in genes correlating with stemness, such as NFκB and EMT. Conclusions: C19MC induces changes in HCC that are consistent with stemness and aggression, which provides a better understanding of why C19MC could be a biomarker of poor prognosis. Full article