ArticleMolecular cancer2020
Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme.
Article in Molecular cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 93 citations in OpenAlex.
- Role of RNA 5‑methylcytosine modification in cancer: Insights from coding and non‑coding RNAs (Review).Molecular medicine reports · 2026Review
- 5-Methylcytosine Analysis of miRNAs in Minimal Change Disease.Biotechnology and applied biochemistry · 2026Article
- mBiology direct · 2026Review
- MicroRNA chemical modifications in post-transcriptional gene silencing and human diseases.Molecular therapy. Nucleic acids · 2025Review
- Recent advances in molecular mechanisms of microRNAs in pathogenesis and resistance of treatment in glioblastoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- LncSNHGs: new targets in osteosarcoma.Cancer gene therapy · 2025Review
- The Life of MicroRNAs: Biogenesis, Function and Decay in Cancer.Biomolecules · 2025Review
- Recent advances in methylation modifications of microRNA.Genes & diseases · 2025Review
- Emerging roles of bases modifications and DNA repair proteins in onco-miRNA processing: novel insights in cancer biology.Cancer gene therapy · 2024Review
- Vitamin C enhances co-localization of novel TET1 nuclear bodies with both Cajal and PML bodies in colorectal cancer cells.Epigenetics · 2024Article
- Ultrafast bisulfite sequencing detection of 5-methylcytosine in DNA and RNA.Nature biotechnology · 2024Article
- Clinician's Guide to Epitranscriptomics: An Example of NLife (Basel, Switzerland) · 2024Review
- The roles and mechanisms of coding and noncoding RNA variations in cancer.Experimental & molecular medicine · 2024Review
- DNAzyme-RCA-based colorimetric and lateral flow dipstick assays for the point-of-care testing of exosomal m5C-miRNA-21.Chemical science · 2024Article
- NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury.Biology direct · 2024Article
- The Mechanisms of miRNAs on Target Regulation and their Recent Advances in Atherosclerosis.Current medicinal chemistry · 2024Review
- miRNA-660-3p inhibits malignancy in glioblastoma via negative regulation of APOC1-TGFβ2 signaling pathway.Cancer biology & therapy · 2023Article
- Small RNA modifications: regulatory molecules and potential applications.Journal of hematology & oncology · 2023Review
- Article
- Crosstalk between Noncoding RNAs and the Epigenetics Machinery in Pediatric Tumors and Their Microenvironment.Cancers · 2023Review
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Authors and funding
16 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiterature reports that mature microRNA (miRNA) can be methylated at adenosine, guanosine and cytosine. However, the molecular mechanisms involved in cytosine methylation of miRNAs have not yet been fully elucidated. Here we investigated the biological role and underlying mechanism of cytosine methylation in miRNAs in glioblastoma multiforme (GBM).
methodsRNA immunoprecipitation with the anti-5methylcytosine (5mC) antibody followed by Array, ELISA, dot blot, incorporation of a radio-labelled methyl group in miRNA, and miRNA bisulfite sequencing were perfomred to detect the cytosine methylation in mature miRNA. Cross-Linking immunoprecipiation qPCR, transfection with methylation/unmethylated mimic miRNA, luciferase promoter reporter plasmid, Biotin-tagged 3'UTR/mRNA or miRNA experiments and in vivo assays were used to investigate the role of methylated miRNAs. Finally, the prognostic value of methylated miRNAs was analyzed in a cohorte of GBM pateints.
resultsOur study reveals that a significant fraction of miRNAs contains 5mC. Cellular experiments show that DNMT3A/AGO4 methylated miRNAs at cytosine residues inhibit the formation of miRNA/mRNA duplex and leading to the loss of their repressive function towards gene expression. In vivo experiments show that cytosine-methylation of miRNA abolishes the tumor suppressor function of miRNA-181a-5p miRNA for example. Our study also reveals that cytosine-methylation of miRNA-181a-5p results is associated a poor prognosis in GBM patients.
conclusionTogether, our results indicate that the DNMT3A/AGO4-mediated cytosine methylation of miRNA negatively.
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