N6-Adenosine Methylation of miRNA-200b-3p Influences Its Functionality and Is a Theranostic Tool

Joséphine Briand; Aurélien A Sérandour; Arulraj Nadaradjane; Gwenola Bougras-Cartron; Dominique Heymann; Benjamin Ory; François M Vallette; Pierre-François Cartron

doi:10.1016/j.omtn.2020.08.010

N6-Adenosine Methylation of miRNA-200b-3p Influences Its Functionality and Is a Theranostic Tool

Mol Ther Nucleic Acids. 2020 Aug 14:22:72-83. doi: 10.1016/j.omtn.2020.08.010. Online ahead of print.

Authors

Joséphine Briand¹, Aurélien A Sérandour², Arulraj Nadaradjane³, Gwenola Bougras-Cartron¹, Dominique Heymann⁴, Benjamin Ory⁵, François M Vallette⁶, Pierre-François Cartron⁷

Affiliations

¹ CRCINA, INSERM, Université de Nantes, Nantes, France; Equipe Apoptose et Progression Tumorale, LaBCT, Institut de Cancérologie de l'Ouest, Saint Herblain, France; Cancéropole Grand-Ouest, Réseau Niches et Epigénétique des Tumeurs (NET), Nantes, France; EpiSAVMEN Network (Région Pays de la Loire), Nantes, France.
² CRCINA, INSERM, Université de Nantes, Nantes, France; Equipe Apoptose et Progression Tumorale, LaBCT, Institut de Cancérologie de l'Ouest, Saint Herblain, France; Cancéropole Grand-Ouest, Réseau Niches et Epigénétique des Tumeurs (NET), Nantes, France; EpiSAVMEN Network (Région Pays de la Loire), Nantes, France; Ecole Centrale Nantes, Nantes, France.
³ CRCINA, INSERM, Université de Nantes, Nantes, France; Equipe Apoptose et Progression Tumorale, LaBCT, Institut de Cancérologie de l'Ouest, Saint Herblain, France; Cancéropole Grand-Ouest, Réseau Niches et Epigénétique des Tumeurs (NET), Nantes, France; EpiSAVMEN Network (Région Pays de la Loire), Nantes, France; LabEX IGO, Université de Nantes, Nantes, France.
⁴ CRCINA, INSERM, Université de Nantes, Nantes, France; Equipe Apoptose et Progression Tumorale, LaBCT, Institut de Cancérologie de l'Ouest, Saint Herblain, France.
⁵ Cancéropole Grand-Ouest, Réseau Niches et Epigénétique des Tumeurs (NET), Nantes, France; EpiSAVMEN Network (Région Pays de la Loire), Nantes, France; INSERM, U1238, Université de Nantes, Nantes, France.
⁶ CRCINA, INSERM, Université de Nantes, Nantes, France; Equipe Apoptose et Progression Tumorale, LaBCT, Institut de Cancérologie de l'Ouest, Saint Herblain, France; LabEX IGO, Université de Nantes, Nantes, France.
⁷ CRCINA, INSERM, Université de Nantes, Nantes, France; Equipe Apoptose et Progression Tumorale, LaBCT, Institut de Cancérologie de l'Ouest, Saint Herblain, France; Cancéropole Grand-Ouest, Réseau Niches et Epigénétique des Tumeurs (NET), Nantes, France; EpiSAVMEN Network (Région Pays de la Loire), Nantes, France; LabEX IGO, Université de Nantes, Nantes, France. Electronic address: pierre-francois.cartron@inserm.fr.

Abstract

MicroRNAs (miRNAs or miRs) play crucial roles in biological and pathological processes. Some miRNAs also appear as promising biomarkers and therapeutic tools. However, the epitranscriptomic regulation of miRNAs is not yet fully elucidated in all of their fields of application. We report that adenosine methylation of miR-200b-3p inhibits its repressive function toward its mRNA targets such as XIAP by blocking the formation of the miRNA/3' UTR^mRNA duplex. Our data indicate that the adenosine methylation of miR-200b-3p is associated with the survival of glioblastoma patients. Collectively, our data support the idea that the adenosine methylation of miR-200b-3p can be used as a prodrug having a selective cytotoxicity against cancer cells (while being harmless to peripheral blood mononuclear cells [PBMCs], astrocytes, neurons, and hepatocytes).

Keywords: adenosine methylation; biomarker; glioblastoma; miRNA methylation; prodrug.