Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 11, 2025

The insulin-like growth factor 2 (IGF2) and H19 are overexpressed in hepatocellular carcinoma (HCC). IGF2-derived miR-483-5p is implicated the development of cancers. Here, we investigated involvement IGF2 overexpression regulation its role HCC. Firstly, effect on expression H19, binding to IGF2/H19 enhancer were evaluated HCC cells. Next, miR-483-5p-mediated activation mechanism Then, by which active mediated activate promoters was studied Finally, MED1 as well malignant phenotype cells vitro vivo evaluated. Mir-483-5p up-regulated P2 mRNA-P4 mRNA resulting Mechanistically, increased recruitment Ago1 Ago2 at then activated transcription eRNA RNA polymerase II p300, further induced chromatin loops formation between via eRNA-MED1-IGF2/H19 complex In this process, promoted miR-483-5p. activating up-regulates DNA loops, thereby promoting progression

Language: Английский

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MicroRNAs in atrial fibrillation – have we discovered the Holy Grail or opened a Pandora’s box?

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 12, 2025

Atrial fibrillation (AF) causes a heavy socio-economic burden on healthcare systems around the globe. Identification of new preventive, diagnostic, and treatment methods is imperative. In recent years, special attention has been paid to microRNAs (miRNAs) as potential regulators AF pathogenesis. Through post-transcriptional regulation genes, miRNAs have shown play crucial roles in AF-related structural electrical atrial remodeling. Altered expression different related proarrhythmic changes duration action potentials fibrosis. clinical studies, miRNA associated with AF, whereas experimental studies manipulation emerged therapeutic approach. It would appear that, advent miRNAs, we may found Holy Grail, that efficient personalized therapy be one step away. Yet, relevance evaluation remains questionable. Studies identified numerous but none them sufficient specificity for AF. MicroRNAs are not gene-specific regulate myriad genes. Cardiac non-cardiac off-target effects thus occur following manipulation. A Pandora’s box might opened these sophisticated molecules. this paper, provide critical analysis experimental, epidemiological mechanistic data linking discuss most promising approaches, emphasize number questions remain answered, identify hotspots future research.

Language: Английский

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miRNAs driving diagnosis, prognosis and progression in Merkel cell carcinoma

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 249, P. 154763 - 154763

Published: Aug. 14, 2023

Language: Английский

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iPSC-derived healthy human astrocytes selectively load miRNAs targeting neuronal genes into extracellular vesicles

Molecular and Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 129, P. 103933 - 103933

Published: April 23, 2024

Astrocytes are in constant communication with neurons during the establishment and maturation of functional networks developing brain. release extracellular vesicles (EVs) containing microRNA (miRNA) cargo that regulates transcript stability recipient cells. Astrocyte released factors thought to be involved neurodevelopmental disorders. Healthy astrocytes partially rescue Rett Syndrome (RTT) neuron function. EVs isolated from stem cell progeny also correct aspects RTT. cross blood-brain barrier (BBB) their is found peripheral blood which may allow non-invasive detection EV as biomarkers produced by healthy astrocytes. Here we characterize miRNA sequence motifs human astrocyte derived (ADEVs). First, induced Pluripotent Stem Cells (iPSC) were differentiated into Neural Progenitor (NPCs) subsequently using a rapid differentiation protocol. iPSC expressed specific markers, displayed intracellular calcium transients secreted ADEVs. miRNAs identified RNA-Seq on ADEVs target gene pathway analysis detected brain immune related terms. The profile was consistent identity, included approximately 80 relatively depleted suggestive passive loading. About 120 enriched motif discovered binding sites for RNA proteins FUS, SRSF7 CELF5. miR-483-5p most significantly This MECP2 expression has been differentially samples RTT patients. Our results identify potential selectively sorted implicate protein dependent mechanisms

Language: Английский

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miRNA as potential biomarkers after liver transplantation: A systematic review

Transplantation Reviews, Journal Year: 2024, Volume and Issue: 38(2), P. 100831 - 100831

Published: Jan. 21, 2024

Liver transplantation is a life-saving therapy for end-stage liver disease patients, but acute cellular rejection (ACR) and graft complications remain significant postoperative challenges. Early accurate diagnosis crucial timely intervention improved patient outcomes, their rely currently on invasive biopsy sampling, thus prompting the search non-invasive Biomarkers. MicroRNA (miRNA) have emerged as promising biomarkers in various pathological conditions, potential utility diagnosing after has gained interest. This systematic review of PubMed, Web Science, ClinicalTrials.gov registry analyzes studies exploring miRNA ACR dysfunction (PROSPERO ID CRD42023465278). The Cochrane Collaboration tool assessing risk bias was employed. Population data, identified dynamic regulation, well event prediction were compared. Data extraction quality assessment performed independently by two reviewers. Thirteen included this review. Various investigated miRNAs upregulated association with rejection, like miR-122, miR-155, miR-181, miR-483-3p, miR-885-5p, demonstrating great biomarker potential. Additionally, several conducted target gene analysis, revealing insights into mechanisms linked to ACR. Moreover, also capable predicting different organ following transplantation, expanding versatility. Remaining challenges include standardization profiling, need functional validation, necessity long-term studies. results highlight specific, transplantation. However, further research needed validate these findings establish standardized diagnostic panels incorporate them clinical practice explore miRNA-based therapies future.

Language: Английский

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Hsa-MiR-483 -3p Regulates the Extracellular Matrix Proteins via TGFβ2/SMAD4 Signaling in the Glucocorticoid-responsive Human Trabecular Meshwork Cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Purpose To investigate the role of hsa-miR-483-3p on regulation extracellular matrix (ECM) in cultured human trabecular meshwork (HTM) cells with known steroid response. Methods Primary cultures HTM responsiveness [GC-responder (GC-R) and GC-Non-responder (GC-NR) cells] were grown coverslip 12-well plate until 80% confluence treated 100 nM dexamethasone (DEX) for 24 h transfected different concentrations synthetic miRNA 483-3p mimic or inhibitor. After 72 post transfection, harvest following experiments: (i) percentage transfection efficiency (ii) RNA isolation qPCR analysis (iii) immunofluorescence staining, (iv) protein Western blotting respectively. All experiments performed triplicate three biological samples (n□=□3). Results GC-R showed significantly higher expression SMAD4 as compared to GC-NR cells. Similarly, DEX treatment up-regulated SMAD4-dependent ECM proteins. The presence a miR-483-3p down-regulated production dose-dependent manner by negatively down- regulating SMAD4/TGF-β2 signalling. inhibition was more pronounced GC- NR Conclusion down-regulation is dependent may play protective mitigating response Using mimics demonstrates therapeutic potential management induced ocular hypertension glaucoma.

Language: Английский

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MicroRNAs and Nonalcoholic Steatohepatitis: A Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14482 - 14482

Published: Sept. 23, 2023

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome caused by fat deposition in hepatocytes. Patients with nonalcoholic steatohepatitis (NASH), an advanced form of NAFLD severe fibrosis, are at high risk for liver-related complications, including hepatocellular carcinoma (HCC). However, the mechanism progression from simple to NASH complex, and previous reports have linked gut microbiota, bile acids, immunity, adipokines, oxidative stress, genetic or epigenetic factors. NASH-related injury involves multiple cell types, intercellular signaling thought be mediated extracellular vesicles. MicroRNAs (miRNAs) short, noncoding RNAs that play important roles as post-transcriptional regulators gene expression been implicated pathogenesis various diseases. Recently, many microRNAs NALFD/NASH, suggesting exosomal miRNAs potential non-invasive sensitive biomarkers involved may therapeutic target molecules. We interested which molecules therapy. summarize targeted associated etiology discuss each miRNA terms its pathophysiology, applications, efficacy biomarker.

Language: Английский

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Overexpression of Igf2-derived Mir483 inhibits Igf1 expression and leads to developmental growth restriction and metabolic dysfunction in mice

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114750 - 114750

Published: Sept. 1, 2024

Language: Английский

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RNA therapeutics for treatment of diabetes

Progress in molecular biology and translational science, Journal Year: 2024, Volume and Issue: unknown, P. 287 - 300

Published: Jan. 1, 2024

Language: Английский

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Site-Blocking Antisense Oligonucleotides as a Mechanism to Fine-Tune MECP2 Expression

RNA, Journal Year: 2024, Volume and Issue: 30(12), P. 1554 - 1571

Published: Oct. 8, 2024

Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations in the methyl-CpG-binding protein 2 ( MECP2 ) gene. Despite its severe phenotypes, studies mouse models suggest that restoring MeCP2 levels can reverse RTT symptomology. Nevertheless, traditional gene therapy approaches are hindered MeCP2's narrow therapeutic window, complicating safe delivery of viral constructs without overshooting threshold for toxicity. The 3′ untranslated region (3′ UTR) plays key role regulation, where factors like miRNAs bind to pre-mRNA and fine-tune expression. Given each miRNA's contribution modest, blocking miRNA binding may represent potential strategy diseases with high dosage sensitivity, RTT. Here, we present series site-blocking antisense oligonucleotides (sbASOs) designed outcompete repressive at UTR. This aims increase patients missense or late-truncating mutations, hypomorphic nature be offset enhanced abundance. Our results demonstrate sbASOs elevate dose-dependent manner SH-SY5Y patient fibroblast cell lines, plateauing projected safe. Confirming vivo functionality, sbASO administration wild-type mice led significant Mecp2 upregulation emergence phenotypes associated overexpression. In T158M neural stem model RTT, treatment significantly increased expression downstream effector brain-derived neurotrophic factor (BDNF). These findings highlight sbASO-based therapies MeCP2-related disorders advocate their continued development.

Language: Английский

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