FN Archimer Export Format
PT J
TI Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme
BT 
AF 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
AS 1:1,2;2:3,4,5,6;3:7;4:1,2,8;5:1,8;6:3,4,5;7:6;8:9;9:2;10:2,8;11:10;12:2,8;13:1,2,8;14:3,4,5,6;15:7;16:1,2,8,11;
FF 1:;2:;3:;4:;5:;6:;7:;8:;9:;10:;11:PDG-RBE-BE-LEX;12:;13:;14:;15:;16:;
C1 RCINA, INSERM, Université de Nantes, Nantes, France
   Faculté de Médecine, Université de Nantes, Nantes, France
   CNRS, UMR 6290, Institut de Génétique et Développement de Rennes (IGdR), F-35043, Rennes, France
   Université Rennes1, UEB, UMS 3480 Biosit, Faculté de Médecine, F-35043, Rennes, France
   Plate-forme Génomique Environnementale et Humaine Biosit, Université Rennes1, F-35043, Rennes, France
   CHU Rennes, Service de Génétique Moléculaire et Génomique, F-35033, Rennes, France
   INSERM, UMR 1238, équipe labellisée ligue 2012, 1 Rue Gaston Veil, 44035, Nantes, France
   LaBCT, Institut de Cancérologie de l’Ouest, Saint Herblain, France
   IRISA Inria Rennes Bretagne Atlantique, équipe GenScale, Campus de Beaulieu, 35042, Rennes, France
   Ifremer, Laboratoire d’Ecotoxicologie, Rue de l’Ile d’Yeu, BP21105, cedex 03 44311, Nantes, France
   Institut de Cancérologie de l’Ouest, CRCINA INSERM U1232, Equipe 9 –Apoptose et Progression tumorale, LaBCT, Boulevard du Pr J Monod, 44805, Saint-Herblain, France
C2 INSERM, FRANCE
   UNIV NANTES, FRANCE
   CNRS, FRANCE
   UNIV RENNES, FRANCE
   UNIV RENNES, FRANCE
   CHU RENNES, FRANCE
   INSERM, FRANCE
   ICO, FRANCE
   INRIA, FRANCE
   IFREMER, FRANCE
   ICO, FRANCE
SI NANTES
SE PDG-RBE-BE-LEX
IN WOS Ifremer UPR
   DOAJ
   copubli-france
   copubli-univ-france
IF 3.693
TC 55
UR https://archimer.ifremer.fr/doc/00610/72196/70980.pdf
   https://archimer.ifremer.fr/doc/00610/72196/70981.pdf
   https://archimer.ifremer.fr/doc/00610/72196/70982.pdf
   https://archimer.ifremer.fr/doc/00610/72196/70983.xlsx
   https://archimer.ifremer.fr/doc/00610/72196/70984.xlsx
   https://archimer.ifremer.fr/doc/00610/72196/70985.zip
   https://archimer.ifremer.fr/doc/00610/72196/70986.xlsx
   https://archimer.ifremer.fr/doc/00610/72196/70987.xlsx
   https://archimer.ifremer.fr/doc/00610/72196/70988.pdf
LA English
DT Article
DE ;miRNA;Cytosine-methylation;Epigenetics;DNMT3A;AGO4;Glioblastoma;Epitranscriptomics
AB 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.
PY 2020
PD FEB
SO Molecular Cancer
SN 1476-4598
PU Springer Science and Business Media LLC
VL 19
IS 1
UT 000519936000002
DI 10.1186/s12943-020-01155-z
ID 72196
ER

EF