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Provedor de dados:  ArchiMer
País:  France
Título:  Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme
Autores:  Cheray, Mathilde
Etcheverry, Amandine
Jacques, Camille
Pacaud, Romain
Bougras-cartron, Gwenola
Aubry, Marc
Denoual, Florent
Peterlongo, Pierre
Nadaradjane, Arulraj
Briand, Josephine
Akcha, Farida
Heymann, Dominique
Vallette, François M.
Mosser, Jean
Ory, Benjamin
Cartron, Pierre-françois
Data:  2020-02
Ano:  2020
Palavras-chave:  MiRNA
Resumo:  Background Literature 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). Methods RNA 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. Results Our 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. Conclusion Together, our results indicate that the DNMT3A/AGO4-mediated cytosine methylation of miRNA negatively.
Tipo:  Text
Idioma:  Inglês

Editor:  Springer Science and Business Media LLC
Formato:  application/pdf
Fonte:  Molecular Cancer (1476-4598) (Springer Science and Business Media LLC), 2020-02 , Vol. 19 , N. 1 , P. 36 (16p.)
Direitos:  info:eu-repo/semantics/openAccess

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