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PubMed2026

Comparative analysis of DDR-related genes and microRNA expression during rice germination: Implications for salinity susceptibility screening.

Soil salinity poses a significant threat to the agri-food sector and particularly to rice cultivation. High salinity during germination induces overproduction of reactive oxygen species (ROS) that cause lesions in the DNA resulting in reduced vigor. MicroRNAs (miRNAs) are known to modulate stress response in plants, however, studies focusing on its relation with the expression of the DNA damage response (DDR)-related genes are not thoroughly explored. In this regard, the aim of this work was to investigate the link between the expression of miRNAs and putative targeted DDR-related genes in response to salinity stress during germination. Eight varieties representative of indica and japonica rice subspecies were categorized into clusters through a principal component analysis (PCA) based on their germination performance and stress tolerance index under varying concentrations of NaCl. Subsequently, the expression patterns of six miRNAs and their putative targeted DDR genes were measured in two contrastive cultivars through quantitative real-time PCR (qRT-PCR) while correlations were examined through Pearson's analysis. Results showed distinct expression profiles between halotolerant and sensitive cultivars. Two miRNAs were further investigated in mature dry seeds of all the cultivars to verify their earliest, seed-specific discriminative potential. The distinct miR414 expression pattern may represent a potential biomarker for identifying salinity-susceptible cultivars during early-stage breeding screening.

Oryza↗

PubMed2026

MicroRNAs in Veterinary Viral Diseases: A Comprehensive Review from Molecular Mechanisms to Clinical Translation.

MicroRNAs (miRNAs) are small non-coding RNA molecules, approximately 22 nucleotides in length, that regulate post-transcriptional gene expression and have emerged as pivotal modulators of host-virus interactions. Veterinary viral diseases continue to pose substantial challenges to animal health, livestock productivity, food security, and public health, particularly due to their zoonotic potential. While miRNA research has advanced considerably, a comprehensive and critically integrated understanding of their biological functions and clinical applications across veterinary viral diseases remains incomplete. This comprehensive critical narrative synthesis addresses four overarching research questions: (1) What conserved and species-specific miRNA-mediated mechanisms govern major veterinary viral diseases? (2) What contextual factors determine antiviral vs. proviral duality? (3) To what extent do circulating miRNA signatures offer diagnostic and prognostic utility? (4) What translational barriers currently prevent clinical implementation, and how can the One Health framework help overcome them? Integrating three interconnected dimensions-molecular mechanisms, pathogen-specific responses, and translational applications-the review synthesizes evidence across PRRSV, avian oncogenic viruses (MDV, ALV), the immunosuppressive IBDV, FMD, BVDV, Ebola, Hendra, Rabies, and aquatic viral diseases. A key contribution of this review is the proposal of a four-axis contextual framework that explains the antiviral/proviral duality of miRNAs, and a 'One miRNA, One Health' convergence model with a concrete implementation roadmap. Key findings include: (a) a four-axis contextual framework (cell type, infection stage, viral strain, host-viral miRNA competition) that explains the antiviral/proviral duality; (b) virus-encoded miRNAs (v-miRNAs) as lower-risk therapeutic targets due to their absence from uninfected host genomes; (c) circulating miRNA biomarkers validated only at proof-of-concept stage (TRL 1-3), with no veterinary product yet at TRL ≥4; and (d) zoonotic conservation of miR-155, miR-146a, miR-21, and miR-122 across human and veterinary pathogens, supporting a 'One miRNA, One Health' convergence strategy. Critical short-term priorities are standardized pre-analytical protocols, open-access veterinary miRNA databases, and multicenter validation in natural infection cohorts.

Antiviral therapy↗

PubMed2025

Genome-wide analysis of host-encoded microRNAs modulating SARS-CoV-2 infection.

Viruses exploit cellular machinery to complete their replication cycle. Furthering our understanding of this process provides insight into the mechanism of virus replication and potential targets for antiviral therapeutics. Genome-wide CRISPR screens have identified cellular pathways important in the SARS-COV-2 infection process, including vesicular traffic, lipid homeostasis and PI3K signalling. Functional genomics-driven analysis of host-encoded microRNAs (miRNAs) impacting SARS-CoV-2 infection would provide further unbiased and discovery-driven insight into the host-pathogen interface. Here we present findings from genome-wide complementary miRNA mimic and inhibitor screens performed in a bio-safety level (BSL)-4 laboratory using a combination of high-throughput robotics, high-content imaging and novel data analysis pipelines. This dataset has identified both miRNA promoters and inhibitors of SARS-CoV-2 replication which may be used by researchers to further explore therapeutic targets against SARS-CoV-2 and the host factors influencing COVID pathogenesis.

MicroRNAs↗

PubMed2017

Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus.

Small non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes. Some miRNAs such as miR-10b that was upregulated in limbus vs. central cornea and in diabetic vs. normal limbus also showed significant increase in T1DM vs. T2DM limbus. Overexpression of miR-10b increased Ki-67 staining in human organ-cultured corneas and proliferation rate in cultured corneal epithelial cells. MiR-10b transfected human organ-cultured corneas showed downregulation of PAX6 and DKK1 and upregulation of keratin 17 protein expression levels. In summary, we report for the first time differential miRNA signatures of T1DM and T2DM corneal limbus harboring LESC and show that miR-10b could be involved in the LESC maintenance and/or their early differentiation. Furthermore, miR-10b upregulation may be an important mechanism of corneal diabetic alterations especially in the T1DM patients.

Adult↗

PubMed2013

MicroRNA-directed program of cytotoxic CD8+ T-cell differentiation.

Acquisition of effector properties is a key step in the generation of cytotoxic T lymphocytes (CTLs). Here we show that inflammatory signals regulate Dicer expression in CTLs, and that deletion or depletion of Dicer in mouse or human activated CD8(+) T cells causes up-regulation of perforin, granzymes, and effector cytokines. Genome-wide analysis of microRNA (miR, miRNA) changes induced by exposure of differentiating CTLs to IL-2 and inflammatory signals identifies miR-139 and miR-150 as components of an miRNA network that controls perforin, eomesodermin, and IL-2Rα expression in differentiating CTLs and whose activity is modulated by IL-2, inflammation, and antigenic stimulation. Overall, our data show that strong IL-2R and inflammatory signals act through Dicer and miRNAs to control the cytolytic program and other aspects of effector CTL differentiation.

Adoptive Transfer↗

PubMed2025

MicroRNA-122 overexpression suppresses the colon cancer cell proliferation by downregulating the astrocyte elevated gene-1/metadherin oncoprotein.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate essential cellular functions, such as cell adhesion, proliferation, migration, invasion, and programmed cell death, and therefore, alterations in miRNAs can contribute to carcinogenesis. Previous studies have shown that miRNA-122 is abundant in the liver and regulates cell proliferation, migration, and apoptosis. However, the expression pattern and mechanism of actions of miR-122 remain primarily unknown in colon cancer. METHODS: In this study, we analyzed The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database to assess the clinical significance of astrocyte elevated gene-1 (AEG-1)/metadherin (MTDH) and miR-122 in colon cancer. MiR-122 overexpression studies were performed in HCT116, SW480, and SW620 cell lines. Dual-luciferase assay was carried out to confirm the interaction between AEG-1 and miR-122. In vivo-JetPEI-transfection reagent was used for in-vivo transient transfection of miR-122 in the AOM/DSS-induced colon tumor mouse model. RESULTS: Our results demonstrate that miR-122 was downregulated in colon cancer cells, and it influences the expressions of apoptotic factors and inflammatory cytokines. MiR-122 overexpression in HCT116, SW480, and SW620 cells showed upregulation of Caspase 3, Caspase 9, and BAX and decreased expression of BCL2, which are pro-apoptotic and anti-apoptotic members that maintain a ratio between cellular survival and cell death. In vivo transient transfection of miR-122 mimic in AOM/DSS induced colon tumor mouse model showed less inflammation and disease activity. The TCGA-COAD data indicated that AEG-1 expression was higher in patients with low expression of miR-122 and lower AEG-1 expression in patients with higher expression miR-122. CONCLUSION: Our findings highlight the key role of miR-122 in the high grade of colonic inflammation, and possibly in colon cancer, and the use of miR-122 mimic might be a therapeutic option.

MicroRNAs↗

PubMed2026

Identification of putative causal associations between MicroRNAs and breast cancer via Mendelian randomization and bioinformatic analysis.

MicroRNAs (miRNAs) are implicated in breast cancer progression and prognosis. This study employed a Mendelian randomization (MR) framework to investigate causal relationships between plasma circulating miRNAs and breast cancer. miRNA expression quantitative trait loci were extracted from 2 independent cohorts. High-confidence miRNAs and their associated single-nucleotide polymorphisms were selected for 2-sample MR analyses using inverse-variance weighted and MR-Egger methods. Differential expression analysis and univariate Cox regression identified survival-associated genes in breast cancer, while enrichment analyses revealed pathways and biological processes linked to candidate targets. Pan-cancer analyses of miRNAs and targets were conducted via the ENCORI platform. Initial MR analyses in the discovery phase identified hsa-miR-100-5p, hsa-miR-125b-5p, and hsa-miR-339-5p as significantly associated with reduced breast cancer risk (P < .05), suggesting potential protective roles. A total of 1291 survival-associated differentially expressed genes were identified, with 39 overlapping targets implicated in miRNA-mediated breast cancer intervention. Enrichment analyses highlighted their involvement in cell cycle regulation and p53 signaling pathway. In the validation cohort, only hsa-miR-339-5p confirmed a protective effect on breast cancer risk, while hsa-miR-100-5p and hsa-miR-125b-5p did not reach significance. Pan-cancer profiling demonstrated aberrant miRNA expression across malignancies, prognostic relevance in multiple cancers, and significant negative correlations between miRNAs and target genes in breast tumors. Our findings provide novel insights into the causal roles of miRNAs in breast cancer pathogenesis and underscore their potential as noninvasive biomarkers and therapeutic targets. Future studies should prioritize functional validation and clinical translation of these miRNAs.

Humans↗

PubMed2026

Suppression of AAV-Delivered Transgene Expression Using Artificial MicroRNAs Delivered by an Alternative AAV Serotype.

Adeno-associated virus (AAV) gene transfer vectors mediate long-term expression in nondividing cells, an advantage for treating chronic disorders. However, current platforms lack a way to selectively shut down transgene expression if adverse effects arise. To create an "off switch," we hypothesized that incorporating unique artificial microRNA (amiRNA) target sequences into an AAV expression cassette would allow subsequent suppression of transgene expression using a second AAV vector encoding the cognate amiRNA. We introduced 22-nt sequences absent from human and mouse transcriptomes into the 3' untranslated region (UTR) of a therapeutic AAV cassette. To identify optimal amiRNAs, two tandem copies of each amiRNA were cloned into the 3'UTR of an mCherry reporter gene. In vitro assessment of six amiRNA/target pairs using a dual luciferase assay identified four amiRNAs that efficiently suppressed reporter expression. Cells cotransfected with target site 3 (TS3) and amiRNA-T3B showed the greatest reduction in luciferase activity (80%, p < 0.0001) and were selected for further study. The "off-switch" system was then evaluated using an AAV5 therapeutic vector expressing a recombinant humanized anti-IgE monoclonal antibody (AAV5-TBG-anti-IgE-TS3), designed for long-term suppression of allergen-induced reactions. Co-transfection of HEK293T cells with anti-IgE-TS3 and amiRNA-T3B significantly reduced anti-IgE mRNA and protein levels relative to a control amiRNA (p < 0.0001). In vivo testing in Balb/c mice (n = 5) involved intravenous administration of AAV5-anti-IgE-TS3 (3.2 × 1010 gc), followed 4 weeks later by an AAVrh.10 amiRNA vector (AAVrh.10-TBG-amiRNA-T3B; 1 × 1011 gc). Control mice receiving only the therapeutic vector expressed 18.4 ± 13.8 µg/mL serum anti-IgE at 10 weeks. In contrast, mice receiving the amiRNA "off" vector showed marked suppression of anti-IgE (0.3 ± 0.15 µg/mL, p < 0.0001). These findings provide proof-of-concept that AAV-delivered amiRNAs can selectively switch off transgene expression, offering a strategy to improve the safety of AAV-mediated gene therapies.

Dependovirus↗

PubMed2024

Use of extracellular vesicle microRNA profiles in patients with acute myeloid leukemia for the identification of novel biomarkers.

OBJECTIVES: This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML. MATERIALS AND METHODS: BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples. RESULTS: We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers. CONCLUSIONS: Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach.

Humans↗

PubMed2026

First insights into the miRNA landscape of Tursiops truncatus milk reveal shared dominant microRNA families with terrestrial mammals.

MicroRNAs (miRNAs) are small non-coding RNAs that play crucial regulatory roles in gene expression in metazoans. While the miRNA repertoire and relative abundances have been extensively studied in terrestrial mammals, no information was available for the milk of marine mammals. Here, we present the first characterization of the miRNA genomic landscape and abundance in milk in the bottlenose dolphin (Tursiops truncatus). Using a sequence-based comparative approach, we identified 186 conserved miRNA families comprising 354 high-confidence precursors in the dolphin genome. Comparative analysis across 52 cetacean genomes revealed a small number of lineage-specific loss events, such as mir-187 in Delphinidae, and the absence of nine miRNA families in all cetaceans. Small RNA sequencing from pooled milk samples confirmed the detectable abundance of 119 miRNAs, with a landscape dominated by mir-148, let-7, mir-8, and mir-21, collectively accounting for over 70% of total miRNA reads. These dominant families include miRNAs frequently reported in the milk of terrestrial mammals, suggesting qualitative similarity in the major milk miRNA repertoire between dolphin and terrestrial mammals. These findings should be interpreted as a first sequencing-supported exploratory characterization of dolphin milk miRNAs.

Animals↗

PubMed2017

MicroRNA‑27a promotes tumorigenesis via targeting AKT in triple negative breast cancer.

Altered microRNA (miRNA/miR) expression regulates tumor development and progression in triple‑negative breast cancer (TNBC). The present study examined the effect of miR‑27a on proliferation, migration and invasion of TNBC cells in vitro and in vivo. An MTT assay was performed to examine the proliferation of MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells with either overexpression of miR‑27a or downregulation of miR‑27a, in the presence or absence of radiation. The migratory and invasive abilities of MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells were assessed by Transwell migration and Matrigel invasion assays. The protein expression levels were examined by western blotting. The caspase‑Glo3/7 assay was performed to examine the effect of miR‑27a on radiation‑induced apoptosis in MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells. A luciferase assay was performed to evaluate the effect of miR‑27a on phosphatase and tensin homolog (PTEN) and B cell lymphoma (Bcl)‑2 associated X, apoptosis regulator (BAX) expression. Immunodeficient nude mice were used to examine tumor growth following injection of MDA‑MB‑231 breast cancer cells. miR‑27a promoted proliferation in vitro and in vivo, and enhanced migration and invasion in TNBC cells. miR‑27a improved the survival of TNBC cells following irradiation. miR‑27a inhibited radiation‑induced apoptosis in TNBC cells by regulation of caspase 3/7 and Bcl‑2 expression. Furthermore, the expression levels of PTEN and phosphorylated protein kinase B in MDA‑MB‑231 and MDA‑MB‑468 cells was altered following overexpression of miR‑27a. The luciferase assay demonstrated that miR‑27a regulated PTEN and BAX expression by binding to 3'‑untranslated regions. Overall, miR‑27a exhibits an essential role in tumor development and progression in TNBC and may be used as a potential biomarker to predict radiotherapy response and prognosis for the disease.

3' Untranslated Regions↗

PubMed2026

MicroRNA-mRNA Networks in Skeletal Muscle of Tailored Pig Models for Dystrophinopathies.

BACKGROUND: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked dystrophinopathies caused by mutations in the dystrophin (DMD) gene. A common DMD-causing mutation in humans is exon 52 deletion (DMDΔ52), which disrupts the reading frame and abolishes dystrophin expression. Therapeutic skipping of exon 51 or 53 can restore the reading frame, producing a truncated but functional protein and generating a BMD-like phenotype. Porcine models recapitulating DMDΔ52 (DMD) and DMDΔ51-52 (BMD-like) were used to identify molecular differences and condition-specific miRNA-mRNA networks. METHODS: Skeletal muscle (triceps brachii) from four DMD, four BMD, and five wild-type (WT) pigs at 3.5 months of age underwent stranded total RNA-seq and small RNA-seq. Differentially expressed mRNAs (|log2FC| ≥ 1, adj. p ≤ 0.05) and miRNAs (adj. p ≤ 0.05) were identified with DESeq2. miRNA-mRNA networks were constructed using RNAhybrid predictions (MFE < -25 kcal/mol, seed pairing) filtered by inverse Pearson correlation. RESULTS: Compared with WT, DMD muscle exhibited 1440 upregulated and 487 downregulated genes, characterized by strong repression of structural, contractile, calcium-handling and metabolic genes (e.g., MYBPC2, MYL3, MYLK2, CACNA2D3, CACNA2D4) and marked upregulation of inflammatory mediators and innate immune receptors (e.g., IL6, IL18, IL1R1, CCR1/2/5, TLR1/2/4/7/9). In contrast, BMD muscle showed partial restoration of these pathways and clustered closer to WT in global expression profiles. Distinct miRNA signatures were observed between DMD and BMD. Differential expression analysis identified 22 upregulated and 12 downregulated miRNAs in DMD versus WT and 36 upregulated and 21 downregulated miRNAs in BMD versus WT. Integration of miRNA and mRNA data yielded extensive regulatory networks (1013 unique pairs for upregulated miRNAs in DMD; 2679 pairs for downregulated miRNAs in BMD). Two condition-specific miRNAs emerged as strong biomarker candidates: ssc-miR-296-3p (upregulated exclusively in DMD, targeting 228 genes enriched in muscle structure and fatty acid metabolism) and ssc-miR-423-5p (elevated specifically in BMD, targeting 67 genes involved in calcium signalling and tissue development). Several dysregulated miRNAs, including miR-199a-5p and miR-199b, overlapped with those reported in human DMD and other muscular dystrophies. CONCLUSIONS: Exon 51 skipping in the DMDΔ52 background partially restores key transcriptional programmes in skeletal muscle but does not fully normalize them to WT patterns. The identification of condition-specific miRNAs highlights post-transcriptional regulatory differences between DMD and BMD, positioning them as promising biomarkers and therapeutic targets. These findings underscore the translational value of porcine dystrophinopathy models for mechanistic studies and preclinical evaluation of RNA-targeted interventions.

Animals↗

PubMed2025

Circulating microRNA panels for multi-cancer detection and gastric cancer screening: leveraging a network biology approach.

BACKGROUND: Screening tests, particularly liquid biopsy with circulating miRNAs, hold significant potential for non-invasive cancer detection before symptoms manifest. METHODS: This study aimed to identify biomarkers with high sensitivity and specificity for multiple and specific cancer screening. 972 Serum miRNA profiles were compared across thirteen cancer types and healthy individuals using weighted miRNA co-expression network analysis. To prioritize miRNAs, module membership measure and miRNA trait significance were employed. Subsequently, for specific cancer screening, gastric cancer was focused on, using a similar strategy and a further step of preservation analysis. Machine learning techniques were then applied to evaluate two distinct miRNA panels: one for multi-cancer screening and another for gastric cancer classification. RESULTS: The first panel (hsa-miR-8073, hsa-miR-614, hsa-miR-548ah-5p, hsa-miR-1258) achieved 96.1% accuracy, 96% specificity, and 98.6% sensitivity in multi-cancer screening. The second panel (hsa-miR-1228-5p, hsa-miR-1343-3p, hsa-miR-6765-5p, hsa-miR-6787-5p) showed promise in detecting gastric cancer with 87% accuracy, 90% specificity, and 89% sensitivity. CONCLUSIONS: Both panels exhibit potential for patient classification in diagnostic and prognostic applications, highlighting the significance of liquid biopsy in advancing cancer screening methodologies.

Neoplasms↗

PubMed2024

ZEB family is a prognostic biomarker and correlates with anoikis and immune infiltration in kidney renal clear cell carcinoma.

BACKGROUND: Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown. METHODS: Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration. RESULTS: It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments. CONCLUSIONS: Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.

Humans↗

PubMed2026

Aldosterone suppresses Na+/H+ exchanger-3 expression through miR-204-5P-mediated posttranscriptional regulation in distal colon.

Na+/H+ exchanger-3 (NHE3) is a major mediator of electroneutral NaCl absorption in the intestine and colon. In the distal colon, chronic aldosterone exposure suppresses NHE3 expression, but the molecular mechanism responsible for this regulation remains unclear. Here, we tested whether aldosterone represses NHE3 through microRNA-dependent posttranscriptional regulation. Transcriptomic analysis of distal colon from dietary Na+-depleted rats identified miR-204-5P (miR-204-5P) as markedly upregulated. Aldosterone increased miR-204-5P abundance and concomitantly reduced NHE3 mRNA, protein expression, and transport activity in rat and human distal colonic epithelium and in SK-CO15 cells. Bioinformatic and reporter analyses identified a conserved miR-204-5P binding site within the NHE3 3'-untranslated region, and miR-204-5P mimic transfection markedly suppressed NHE3 expression and transport activity without affecting other Na+/H+ exchanger isoforms. These findings identify a previously unrecognized aldosterone-microRNA signaling pathway that mediates chronic repression of NHE3 and provide new insight into hormonal regulation of colonic Na+ absorption.NEW & NOTEWORTHY This study identifies a previously unrecognized aldosterone-microRNA signaling mechanism regulating colonic Na+ absorption. We demonstrate that aldosterone induces miR-204-5P, which directly targets the NHE3 3'-untranslated region and suppresses NHE3 expression and transport activity in distal colonic epithelium. These findings reveal a microRNA-mediated pathway linking mineralocorticoid signaling to long-term inhibition of electroneutral NaCl absorption, providing new insight into hormonal regulation of intestinal electrolyte transport.

Animals↗

PubMed2026

miRNA-mediated control of TLR-NLR interplay in the uterus: A hidden corner of recurrent pregnancy loss.

Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are crucial pattern recognition receptors that initiate inflammatory responses and immunological activation upon detecting pathogen- or damage-associated molecular patterns (PAMPs/DAMPS) in the female reproductive tract, thereby maintaining homeostasis and supporting pregnancy success. Their signaling pathways play a significant role in reproductive disorders by mediating the immune response to various pathogenic stimuli. Recurrent pregnancy loss (RPL), defined as the natural ending of two or more pregnancies before 24 weeks of gestation, approximately half of these patients remain idiopathic without precise prognostic, diagnostic, and therapeutic plans. Emerging data point that microRNAs are essential for immunological control in the female reproductive tract. MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to mRNA and preventing translation into protein. miRNAs play a role in many biological processes, including the development and differentiation of trophoblasts, the activation and implantation of embryos, immune tolerance, and the receptivity of the endometrium during implantation. Given their capacity to regulate up to 30 % of the human genome, miRNAs offer a promising avenue for understanding the immunopathogenesis of pregnancy complications. Recent research has detected differential expression of specific miRNAs in reproductive system pathologies. This review focuses on microRNAs and their association with idiopathic recurrent miscarriage, a condition characterized by considerable heterogeneity. Future studies identifying the precise mechanisms linking miRNA-mediated immune dysregulation in RPL immunopathogenesis could open the way for novel personalized therapeutic and diagnostic strategies.

Female↗

PubMed2025

Bioinformatic analyses and validated experiments reveal an aging hallmark gene set and protective miR of coronary artery disease.

To investigate how aging hallmarks exert roles in the age-related disease of coronary artery disease (CAD). R software and the GEO2R online tool identified differentially expressed genes (DEGs) and differentially expressed microRNAs (DEMis) in CAD microarray datasets from the Gene Expression Omnibus. Genes common to target genes of DEMis, DEGs, and an aging gene list from Human Aging Genomic Resources were then identified and analyzed for protein-protein interactions and functional and pathway enrichment. An miR-mRNA network was constructed using Cytoscape. Receiver operating characteristic curve analysis assessed the diagnostic utility of DEMis in CAD. The expression of two DEMis from a CAD cohort was employed to validate the findings. An aging hallmark gene set, comprising 18 genes, was delineated, with the hub gene TP53 established through protein-protein interaction and microRNA-mRNA networks. Within the microRNA-mRNA network, two DEMis (hsa-miR-423-5p and hsa-miR-564) potentially regulated TP53, rendering them potential CAD biomarkers, as indicated by their area under the curves (AUC) surpassing 0.6. Validation experiments corroborated an AUC of 0.7002 for hsa-miR-423-5p and 0.7261 for hsa-miR-564, highlighting its protective association with CAD. Combining hsa-miR-423-5p, hsa-miR-564, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), white blood cells (WBC) achieved an area under the receiver operating characteristics curve of 0.783. A CAD-associated gene set was identified, with TP53 as the central hub. Hsa-miR-564 emerged as a potential protective factor against CAD.

Humans↗

PubMed2025

Investigating the miRNA-mRNA interactome of human trabecular meshwork cells treated with TGF-β1 provides insights into the pathogenesis of pseudoexfoliation glaucoma.

Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome. Primary human trabecular meshwork cells originating from normal donors were treated with TGF-β1 at 5 ng/mL for 24h; total RNA was extracted followed by RNA-Seq and miRNA-Seq. For both mRNA and miRNA species, differential expression was determined using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts, edgeR (for miRNA) and DESeq2 (for mRNA). Putative mRNA-miRNA interactions between differentially expressed mRNA and miRNA species were determined using interaction databases miRWalk, miRTarBase, TarBase and TargetScan. To classify mRNA species by function and pathway, gene enrichment was performed using Enrichr. The resulting miRNA-mRNA interactome consisted of 1202 interactions. Some highly connected microRNAs were hsa-let-7e-5p, hsa-miR-20a-5p, hsa-miR-122-5p, and hsa-miR-29c-3p. Most differentially expressed genes were indicated to be regulated by miRNAs. The sub-interactomes of genes involved in specific pseudoexfoliation glaucoma related enrichment terms such as oxidative stress, unfolded protein response, signal molecules and ECM remodelling were determined. This is the first study to present a genome-wide microRNA-mRNA regulatory network for human trabecular meshwork cells treated with TGF-β1 and may serve to generate unbiased hypotheses about regulatory functions and mRNA targets of miRNAs in pseudoexfoliation glaucoma and may help to develop miRNA-based therapeutics.

Humans↗