SEARCH · Search PubMed

Results for “microRNA expression”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2026

MicroRNAs and predicted targets in the switch from monolayered to spheroids of cholangiocarcinoma cells.

BACKGROUND: Extrahepatic cholangiocarcinoma (eCCA) is characterized by marked molecular heterogeneity and limited therapeutic options. MicroRNAs (miRNAs) are key post-transcriptional regulators of cancer-related pathways, but their contribution to tumor adaptation in physiologically relevant models remains poorly understood. Three-dimensional (3D) tumor spheroids better mimic in vivo conditions than conventional two-dimensional (2D) cultures. METHODS: We compared miRNA expression profiles in two eCCA cell lines (Sk-ChA-1 and Mz-ChA-1) grown as monolayers (2D) or multicellular tumor spheroids (3D). MiRNA profiling was performed using NanoString technology. Predicted targets were analyzed by over-representation analysis, and selected miRNAs and genes were validated by RT-qPCR and ELISA-based assays. RESULTS: 3D growth induced extensive miRNA remodeling, with distinct (54 deregulated in Sk-ChA-1 and 29 in Mz-ChA-1 cells) and partially overlapping signatures (miR-1283, miR-577, and miR-2113). Among the shared miRNAs, predicted targets included DUSP10 and RBFOX1, while in spheroids, cell-specific multiple miRNAs converged on shared targets (TNRC6B, SMARCAD1, ATG14, HMGA2, and CLOCK) displaying inverse expression patterns. The transcriptional program impacted MAPK signaling, enhanced EMT, and activated stress-adaptive networks but attenuated proliferation in 3D Sk-ChA-1 cells, while Mz-ChA-1 cells retained a more epithelial and proliferative profile. In this context, we point out the involvement of miR-19b-3p using anti-miR transfection experiments. CONCLUSION: Our findings reveal a miRNA-driven regulatory landscape associated with 3D growth in eCCA, linking tumor architecture to signaling rewiring and cellular plasticity, and highlight potentially druggable candidate targets and pathways to investigate as candidates using inhibitors or gene therapy-based interventions.

Humans↗

PubMed2026

Screening and identification of the ncRNA-mRNA regulatory network associated with DNA methylation in goose embryonic myoblasts.

BACKGROUND: Local goose breeds Shitou and Wuzong exhibit distinct growth rates, implying divergent embryonic muscle development. This study used embryonic myoblasts from the Magang goose, an established model with superior growth traits, to explore the underlying common regulatory mechanisms. Extending our previous findings that 5-AZA (DNA methylation inhibitor) and BC339 (DNA hydroxylation inhibitor) oppositely affect myoblast proliferation and differentiation, we performed whole-transcriptome sequencing on inhibitor-treated goose embryonic myoblasts. This aimed to identify DNA methylation-mediated ncRNA-mRNA networks governing myoblast fate, with key interactions being functionally validated. RESULT: 5-AZA significantly promotes cell proliferation and differentiation by inhibiting DNA methyltransferase activity and reducing DNA methylation levels, whereas BC339 significantly suppresses cell proliferation and differentiation by inhibiting demethylation and increasing DNA methylation levels. Specifically, we identified 6,309 mRNAs, 579 lncRNAs, 194 miRNAs, and 825 circRNAs that were differentially expressed in response to 5-AZA and BC339 treatment. Based on GO and KEGG enrichment analyses, differentially expressed genes related to muscle development were selected to construct a ceRNA network. This network comprises 5 differentially expressed lncRNAs (DELs: MSTRG.17572.1, XR_001211738.1, MSTRG.1886.1, XR_001212555.1, MSTRG.8995.2), 2 differentially expressed circRNAs (DECs: novel_circ_029953, novel_circ_017636), 11 differentially expressed miRNAs (DEMs: miR-383-x, miR-10174-y, miR-191-x, miR-24-x, miR-9619-y, novel-m0303-5p, novel-m0105-3p, miR-204-x, miR-211-z, novel-m0075, miR-26-y), 5 differentially expressed genes (DEGs: KIF3A, CCND1, PPM1A, Table 2, TGFBR1), forming a total of 24 interactions. This study identified miR-9619-y as a critical negative regulator of goose embryonic myoblast development through targeted inhibition of CCND1. Dual-luciferase reporter assays confirmed the direct binding of miR-9619-y to the 3'-untranslated region of CCND1. Functional experiments demonstrated that overexpression of miR-9619-y significantly reduced the EdU-positive cell ratio and myotube area percentage, accompanied by cell cycle arrest at the G0/G1 phase. Conversely, inhibition of miR-9619-y promoted myoblast proliferation and differentiation while decreasing the proportion of cells in G0/G1 phase. During the proliferation stage, miR-9619-y overexpression significantly suppressed CCND1 expression at both mRNA and protein levels, down-regulated MyoD expression, and reduced Myf5 mRNA abundance; whereas miR-9619-y inhibition up-regulated these genes and their corresponding proteins. During the differentiation stage, overexpression of miR-9619-y similarly decreased the mRNA levels of CCND1, Myh1, and MyoG, as well as the protein levels of MyHC and CCND1, with inhibition producing the opposite effects. CONCLUSION: In this study, we predicted a ceRNA network based on bioinformatics analysis governing goose embryonic myoblast development, identifying key molecular components including mRNAs, miRNAs, lncRNAs, and circRNAs, along with 24 regulatory axes. Functional experiments further demonstrated that miR-9619-y arrests cell cycle progression and negatively regulates the proliferation and differentiation of goose embryonic myoblasts, as evidenced by its impact on both the mRNA and protein expression of key myogenic factors through targeted inhibition of CCND1. These findings, together with the bioinformatically predicted ceRNA network, suggest potential complex post-transcriptional regulatory mechanisms underlying myogenesis in geese and offer candidate molecular targets for genetic improvement of meat production performance in waterfowl breeding programs.

Animals↗

PubMed2026

miR-6388 regulates granulosa cell function in sheep by targeting GDF9 and modulating the TGF-β signaling pathway.

Litter size is an economically important trait in sheep and is closely associated with ovarian follicular development and granulosa cell (GC) function. This study investigated the association between GDF9 polymorphisms and litter size, and examined the post-transcriptional regulation of GDF9 by miR-6388 in ovine GCs. Variants were initially identified by Sanger sequencing in 20 ewes, and subsequently genotyped in 377 three-year-old ewes, including 231 Sonid (SN) sheep and 146 Ujimqin (UM) sheep for association analysis. Candidate miRNAs targeting litter size-associated variants in the GDF9 3'UTR were predicted, and the miR-6388-GDF9 interaction was evaluated using dual-luciferase reporter assays. RT-qPCR, Western blotting, EdU incorporation, and flow cytometry were used to assess endogenous GDF9 expression and GC function. Twelve single-nucleotide polymorphisms were identified, including the putatively novel variant g.42114076C > G. The linkage disequilibrium block comprising g.42116936C > T, g.42113821T > A, and g.42113962G > A polymorphisms of GDF9 was significantly associated with litter size in both SN and UM sheep, whereas the c.477G > A was associated with litter size only in UM sheep. Reporter assays showed that the GDF9 3'UTR region carrying the G allele of g.42113962G > A was more responsive to miR-6388-mediated repression than the region carrying the A allele. miR-6388 overexpression reduced GDF9 mRNA and GDF9 protein levels, inhibited GC proliferation, altered cell-cycle distribution, and promoted apoptosis, whereas miR-6388 knockdown increased GDF9 expression and GC proliferation and reduced apoptosis. These cellular changes were accompanied by altered expression of cell-cycle and apoptosis-related genes and TGF-β signaling-related components.

Animals↗

PubMed2026

Characterization of ZIC5 expression in esophageal squamous cell carcinoma and its association with patient survival.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.

ESCC↗

PubMed2026

Dual Mechanisms Underlie the Repression of Repressor Element 1-Silencing Transcription Factor Expression in Lung Neuroendocrine Carcinoma Cells.

Recent advances in genetic analysis have led to further subtyping of small-cell lung carcinoma (SCLC). The major subtypes of SCLC are the achaete-scute family bHLH transcription factor 1 (ASCL1)-predominant (SCLC-A), neuronal differentiation 1 (NEUROD1)-predominant (SCLC-N), and POU class 2 homeobox 3 (POU2F3) (SCLC-P) subtypes. SCLC-A and SCLC-N tumors express chromogranin A (CHGA) and synaptophysin (SYP), but SCLC-P tumors do not. Large-cell neuroendocrine carcinoma, another type of neuroendocrine carcinoma (NEC), also frequently expresses CHGA and SYP. Because CHGA and SYP expression is controlled by a transrepressor, repressor element 1-silencing transcription factor (REST), the mechanisms underlying REST suppression in NEC were investigated, with a focus on miRNAs and epigenetics, to determine the causes of the differences in the expression of CHGA and SYP between SCLC-A/N and SCLC-P cells. The results showed that miR-375-3p, which was induced by ASCL1 and NEUROD1, repressed REST expression by binding to the 3'-untranslated region of REST mRNA. Bisulfite sequencing and experiments using a DNA methyltransferase inhibitor, a histone deacetylase inhibitor, and chromatin immunoprecipitation-based quantitative PCR revealed that promoter/enhancer hypermethylation and histone deacetylation causes REST gene inactivation in SCLC-A/N. These phenomena were also observed in a large-cell neuroendocrine carcinoma cell line that expressed high levels of ASCL1 and NEUROD1. Taken together, these findings suggest that NEC has dual repressive effects on REST expression, resulting in strict regulation of the expression of CHGA, SYP, and other REST-controlled neuronal/neuroendocrine-specific genes.

Humans↗

PubMed2026

Comparative transcriptome analysis reveals ncRNA-mediated regulatory networks associated with muscle crispiness in grass carp.

Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.

Animals↗

PubMed2021

ERBB3 overexpression due to miR-205 inactivation confers sensitivity to FGF, metabolic activation, and liability to ERBB3 targeting in glioblastoma.

In glioblastoma (GBM), the most frequent and lethal brain tumor, therapies suppressing recurrently altered signaling pathways failed to extend survival. However, in patient subsets, specific genetic lesions can confer sensitivity to targeted agents. By exploiting an integrated model based on patient-derived stem-like cells, faithfully recapitulating the original GBMs in vitro and in vivo, here, we identify a human GBM subset (∼9% of all GBMs) characterized by ERBB3 overexpression and nuclear accumulation. ERBB3 overexpression is driven by inheritable promoter methylation or post-transcriptional silencing of the oncosuppressor miR-205 and sustains the malignant phenotype. Overexpressed ERBB3 behaves as a specific signaling platform for fibroblast growth factor receptor (FGFR), driving PI3K/AKT/mTOR pathway hyperactivation, and overall metabolic upregulation. As a result, ERBB3 inhibition by specific antibodies is lethal for GBM stem-like cells and xenotransplants. These findings highlight a subset of patients eligible for ERBB3-targeted therapy.

Antibodies↗

PubMed2026

Tumor Suppressive Role of Hsa-miR-328-3p in Colon Cancer by Regulating EN2.

BACKGROUND/AIM: Colon cancer is a prevalent and life-threatening malignancy worldwide. Recent studies have focused on how microRNAs (miRNAs) act as post-transcriptional modulators in colon cancer progression. Herein, this study aimed to identify the impact of miRNAs that are decreased in colon cancer and to investigate their regulatory mechanisms. MATERIALS AND METHODS: Differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were identified through analysis of miRNA sequencing and RNA sequencing data from normal and tumor tissues in The Cancer Genome Atlas (TCGA). Expression levels were validated by quantitative polymerase chain reaction (qPCR) in both tissues and cell lines. Functional effects of miRNAs were evaluated by assessing cell viability, proliferation, migration, and invasion following transfection with miRNA mimics. RESULTS: Analysis of miRNA-seq data from the TCGA database identified hsa-miR-328-3p as a miRNA consistently downregulated across all stages of colon cancer. This downregulation was independently validated in colon cancer patient tissues by qPCR. Functional assays demonstrated that enforced expression of hsa-miR-328-3p significantly reduced cell viability, proliferation, migration, and invasion in colon cancer cell lines, supporting its tumor-suppressive role. To elucidate the molecular mechanism underlying these inhibitory effects, target gene analysis was performed. Engrailed homeobox 2 (EN2) was identified as a potential target of hsa-miR-328-3p, and a dual-luciferase assay confirmed that EN2 is directly regulated by hsa-miR-328-3p. CONCLUSION: Collectively, these findings indicate that hsa-miR-328-3p is frequently downregulated in colon cancer and functions as a tumor suppressor by negatively regulating its target gene, EN2, thereby contributing to colon cancer malignancy. EN2 may serve as a potential diagnostic biomarker for colon cancer, while restoration of hsa-miR-328-3p expression represents a promising therapeutic strategy. Further studies are needed to clarify the precise molecular mechanisms linking the hsa-miR-328-3p/EN2 axis to colon cancer progression.

Humans↗

PubMed2026

Semaglutide treatment in MOSH is associated with altered DNA methylation patterns of genes related to glycolipid metabolism.

Male obesity-associated secondary hypogonadism(MOSH) is a common disease among severely obese male patients. Although surgical interventions have demonstrated clinical benefits, a subset of patients continue to experience MOSH following surgery. Therefore, this study aims to investigate epigenetic changes associated with the use of the weight-loss drug Semaglutide in MOSH, focusing on DNA methylation and miRNA expression. In this exploratory study, samples were classified into three groups: a control group (n = 2), a MOSH group (n = 7), and a follow-up group (n = 4). DNA methylation analysis was performed on all samples, while miRNA sequencing was conducted on a subset of the samples: 2 from the control group, 7 from the MOSH group, and 2 from the follow-up group. Differentially expressed miRNAs (DEMs) were analyzed through the R package "limma", and the methylation level of CpG sites was analyzed based on the methylation β value, obtaining differentially methylated genes (DMGs). The functional enrichment analysis of miRNA target genes and methylation change genes was conducted using the R package "clusterProfiler". Finally, the regulatory networks of miRNA and methylation genes as well as the protein-protein interaction (PPI) network were analyzed. A total of 6 DEMs were screened out. The target genes of these DEMs were mainly enriched in pathways such as ATP binding, phosphorylation, cell adhesion, and Glycosphingolipid biosynthesis. Eighty DMGs were identified, and the largest number of DMGs were found in the X chromosome. In the regulatory network of DMGs and DEMs, hsa-miR-423-5p regulates most of these DMGs. Moreover, the PPI network shows that DPP6, DPP10, CACNA1C, and CNTNAP2 are the proteins with the strongest connectivity. Notably, differential CpG methylation changes were observed on chromosome 7, indicating a potential region of epigenetic alteration in MOSH; however, the biological and functional relevance of these changes remains unclear. Collectively, these findings suggest that Semaglutide treatment in MOSH may be associated with concurrent alterations in DNA methylation and miRNA expression, implicating genes related to energy and glycolipid metabolism, including DPP6, DPP10, CACNA1C, and CNTNAP2. These results are exploratory and hypothesis-generating, providing preliminary observations to inform future validation studies.

Semaglutide↗

PubMed2026

Expression profiles of miRNAs in ruminant intermediate hosts with cystic echinococcosis.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a parasitic zoonotic disease recognized by the World Health Organization as a neglected tropical disease of significant public health concern. Despite ongoing control programs, CE remains endemic, underlining the need for integrated control strategies that involve new diagnostic and therapeutic tools. Recent investigations have spotlighted microRNAs (miRNAs) as key regulators in parasite development, immunomodulation, and as potential diagnostic and therapeutic targets. In the present research, a molecular study was conducted to investigate hydatid cyst samples (protoscoleces and germinal membranes) collected in southern Italy from different ruminant species (sheep, cattle, and water buffaloes), naturally infected with CE, with the ultimate goal of establishing a more comprehensive picture of miRNA expression patterns in these intermediate hosts. The bioinformatic analysis of hydatid cyst samples revealed 168 mature miRNAs. Among these, egr-miR-10-5p, egr-let-7-5p, and egr-miR-71-5p were the most abundant, with egr-miR-10-5p showing particularly high expression levels. No significant differences in miRNA abundance between host species were found. In contrast, when focusing on the comparison between protoscoleces and sterile germinal membranes, 24 miRNAs were found to be differentially expressed. Targeted qPCR of four selected miRNAs (egr-miR-71-5p, egr-let-7-5p, egr-miR-125-5p, and egr-miR-10-5p) showed clear overexpression in protoscoleces and in fertile germinal membranes compared with sterile ones. The differential miRNA expression patterns provide insight into the molecular mechanisms controlling the parasite's lifecycle and may guide the development of novel intervention methods to enhance CE control in endemic areas.

Animals↗

PubMed2026

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans↗

PubMed2025

MicroRNAs signatures in small extracellular vesicles for psychological resilience in young adults using machine learning.

AIMS: Psychological resilience refers to an individual's capacity to adapt to adverse events. MicroRNAs (miRNAs) play a crucial role in regulating post-transcriptional processes, while small extracellular vesicles (sEVs) act as transport vehicles. This study aimed to employ genome-wide profiling to identify and validate differences in the expression of resilience-associated sEV-miRNAs between low resilience (LR) and high resilience (HR) in young adults. METHODS: Eighty participants were divided into LR or HR based on the Connor - Davidson Resilience Scale (CD-RISC). The expression levels of the target sEV-miRNAs in LR and HR were compared and analyzed. RESULTS: Expression analyses demonstrated significant differences in let-7b, miR-151b, miR-335, and miR-193a between LR and HR (p < 0.01), with let-7b showing the highest discriminative ability. The AUC values for each sEV-miRNA ranged from 0.74 to 0.94, based on logistic regression and three machine learning models: random forest, support vector machine, and eXtreme gradient boosting. Based on leave-one-out cross-validation in different models, the combined four sEV-miRNAs demonstrated strong performance for detecting LR (AUC = 0.87-0.90). Sex-specific differences were also observed, with female participants showing more pronounced resilience signatures in targeted sEV-miRNAs. CONCLUSIONS: These findings suggest that sEV-miRNAs hold potential as biomarkers for psychological resilience in young adults.

Humans↗

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

Single-cell multiomics reveals exosome-mediated reprogramming and clonotypic remodeling of T cells in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive and immunogenic subtype lacking targeted therapies. While tumor-derived exosomes are known to modulate immune function, their direct impact on human T cell plasticity and antigen specificity remains poorly defined. Here, we conducted a comprehensive single-cell multiomic analysis of primary human T cells exposed to exosomes derived from 17 genomically diverse TNBC cell lines and 35 patient samples. Integrating single-cell RNA-seq, V(D)J sequencing, non-coding RNA profiling, bulk and single-cell cytokine analyses, we uncovered conserved and subtype-specific immunomodulatory programs induced by TNBC exosomes. Exosome-treated T cells displayed skewing toward regulatory and dysfunctional phenotypes, including Th17-like, Treg, and PD-1⁺/PD-L1⁺ Tfh cells. Functional profiling revealed suppression of early activation markers and cytokine responses, alongside selective preservation of cytotoxic features in γδ T and NKT subsets. Transcriptomic and miRNA network analyses demonstrated widespread downregulation of immune effector genes (e.g., HBEGF and TNFSF9) mediated by exosome-delivered regulatory miRNAs (has-miR-98-5p). Notably, exosome-stimulated T cells displayed distinct clonotypic expansions, characterized by the emergence of five tumor-specific γδ TCR clonotypes and 30 unique αβ TCR CDR3 sequences that were absent in mock-treated controls, underscoring the role of exosomes in shaping TCR repertoire dynamics.

Humans↗

PubMed2018

Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone.

Corticosteroids are highly prescribed and effective anti-inflammatory drugs but the burden of side effects with chronic use significantly detracts from patient quality of life, particularly in children. Developing safer steroids amenable to long-term use is an important goal for treatment of chronic inflammatory diseases such as Duchenne muscular dystrophy (DMD). We have developed vamorolone (VBP15), a first-in-class dissociative glucocorticoid receptor (GR) ligand that shows the anti-inflammatory efficacy of corticosteroids without key steroid side effects in animal models. miRNAs are increasingly recognized as key regulators of inflammatory responses. To define effects of prednisolone and vamorolone on the muscle miRNAome, we performed a preclinical discovery study in the mdx mouse model of DMD. miRNAs associated with inflammation were highly elevated in mdx muscle. Both vamorolone and prednisolone returned these toward wild-type levels (miR-142-5p, miR-142-3p, miR-146a, miR-301a, miR-324-3p, miR-455-5p, miR-455-3p, miR-497, miR-652). Effects of vamorolone were largely limited to reduction of proinflammatory miRNAs. In contrast, prednisolone activated a separate group of miRNAs associated with steroid side effects and a noncoding RNA cluster homologous to human chromosome 14q32. Effects were validated for inflammatory miRNAs in a second, independent preclinical study. For the anti-inflammatory miRNA signature, bioinformatic analyses showed all of these miRNAs are directly regulated by, or in turn activate, the inflammatory transcription factor NF-κB. Moving forward miR-146a and miR-142 are of particular interest as biomarkers or novel drug targets. These data validate NF-κB signaling as a target of dissociative GR-ligand efficacy in vivo and provide new insight into miRNA signaling in chronic inflammation.

Animals↗

PubMed2025

miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway.

BACKGROUND: The most common malignant type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The expression levels of hyaluronan-mediated motility receptor (HMMR) in many tumor types are significantly elevated. HMMR is closely associated with tumor-related progression, treatment resistance, and poor prognosis, and has yet to be fully investigated in terms of its expression patterns and molecular mechanisms of action in ccRCC. Further research is imperative to elucidate these aspects. METHODS: We used The Cancer Genome Atlas (TCGA) database to preliminarily investigate HMMR expression and function in ccRCC and the data for 19 samples from the NCBI GEO database (GSE207493) for single-cell analysis. We assessed the differential expression level of HMMR between ccRCC cancerous tissues and their matched non-tumor tissues. Subsequently, a series of in vivo and in vitro experiments were designed to elucidate the biological function of HMMR in ccRCC, including Transwell assays, CCK-8 assays, clone formation assays and subcutaneous xenograft experiments in nude mice. Through bioinformatics analysis, we identified potential microRNAs (miRNAs) that may regulate HMMR, as well as the possible signaling pathways involved. Finally, we conducted a series of cellular functional experiments to validate our hypotheses regarding the HMMR axis. RESULTS: HMMR expression was significantly up-regulated in tumor tissues of ccRCC patients, and elevated HMMR expression level showed a strong correlation with ccRCC progression and adverse prognoses of patients. Knocking down HMMR inhibited the proliferative and migratory abilities of ccRCC cells, while its overexpression amplified these oncogenic properties. In nude mice model, reduced HMMR expression inhibited ccRCC tumor proliferation in vivo. Furthermore, overexpression of an upstream transcriptional regulator, miR-9-5p, effectively downregulated HMMR expression and thus impeded ccRCC cells proliferation and migration. HMMR might influence ccRCC growth via the Epithelial-Mesenchymal Transition (EMT) pathway and the Janus Kinase 1/Signal Transducer and Activator of Transcription 1 (JAK1/STAT1) pathway. CONCLUSIONS: HMMR is overexpressed in ccRCC, and there is a significant link between high HMMR expression and tumor progression, as well as poor patient prognosis. Specifically, HMMR could be targeted and inhibited by miR-9-5p and might modulate the tumorigenesis and progression of ccRCC through both EMT and JAK1/STAT1 signaling pathway.

Carcinoma, Renal Cell↗

PubMed2026

miR-335-3p acts as a tumor suppressor in esophageal squamous cell carcinoma and predicts favorable prognosis.

BACKGROUND: Esophageal cancer is a highly invasive malignancy that severely impairs normal digestive function and poses a substantial threat to patient survival. The pathogenesis of miRNA-mediated tumors has been widely documented. AIM: Verifying the involvement of miR-335-3p in the pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: The study enrolled 90 ESCC patients, from whom clinical data and pathological tissue samples were acquired. The prognostic potential of dysregulated miR-335-3p in ESCC was assessed using the Kaplan-Meier method. miR-335-3p and GFPT1 expression in the specimens were measured by RT-qPCR. Cellular biological functions were verified through transfection, CCK-8, Transwell, and kit-based assays. The targeting relationship was ascertained by luciferase activity assays. RESULTS: miR-335-3p was downregulated in ESCC, which is indicative of poorer prognostic outcomes. GFPT1 was up-regulated and was regarded as a target of miR-335-3p. Increased miR-335-3p levels markedly impaired cellular biological functions. Conversely, simultaneous overexpression of GFPT1 alleviated the negative effects induced by miR-335-3p mimic, which was associated with the partial restoration of cell activity and antioxidant capacity. CONCLUSION: miR-335-3p represents a potential independent prognostic marker in ESCC. The anti-tumor activity induced by miR-335-3p overexpression may be associated with its regulation of GFPT1.

Humans↗

PubMed2025

Genome imbalance modulates the expression of long non-coding RNAs in maize.

Genome imbalance, resulting from varying the dosage of individual chromosomes (aneuploidy), has a more detrimental effect than changes in complete sets of chromosomes (haploidy/polyploidy). This imbalance is likely due to disruptions in stoichiometry and interactions among macromolecular assemblies. Previous research has shown that aneuploidy causes global modulation of protein-coding genes (PCGs), microRNAs, and transposable elements (TEs), affecting both the varied chromosome (cis-located) and unvaried genome regions (trans-located) across various taxa. While long non-coding RNAs (lncRNAs) are important gene expression regulators, their roles in the context of genomic imbalance remain largely unexplored. In this study, we analyzed and compared the impact of aneuploidy and haploidy/polyploidy on lncRNA expression using RNA-seq data from maize mature leaf tissue. Our results indicate that cis-located lncRNAs are modulated from dosage compensation to a gene dosage effect, while trans-located lncRNAs exhibit trends ranging from an inverse effect to a positive correlation with chromosomal dosage. Remarkably, the ploidy series showed a lesser degree of lncRNA modulation. LncRNAs and TEs display a similar trend of inverse modulation but exhibit greater sensitivity to dosage changes compared to PCGs. The construction of cis-acting and trans-acting lncRNA co-expression networks indicates that lncRNAs likely function as dosage-sensitive regulators of gene expression under conditions of genomic imbalance. Overall, this study not only elucidates the dosage effect of plant lncRNAs but also serves as a valuable resource for exploring potential regulators of PCGs that play significant biological functions.

Zea mays↗