Briand Joséphine, Sérandour Aurélien A, Nadaradjane Arulraj, Bougras-Cartron Gwenola, Heymann Dominique, Ory Benjamin, Vallette François M, Cartron Pierre-François
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.
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.
Mol Ther Nucleic Acids. 2020 Aug 14;22:72-83. doi: 10.1016/j.omtn.2020.08.010.
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 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).
微小RNA(miRNA或miR)在生物和病理过程中发挥着关键作用。一些miRNA也有望成为生物标志物和治疗工具。然而,miRNA的表观转录组调控在其所有应用领域中尚未完全阐明。我们报告称,miR-200b-3p的腺苷甲基化通过阻断miRNA/3'UTR双链体的形成,抑制其对XIAP等mRNA靶标的抑制功能。我们的数据表明,miR-200b-3p的腺苷甲基化与胶质母细胞瘤患者的生存率相关。总体而言,我们的数据支持这样一种观点,即miR-200b-3p的腺苷甲基化可作为一种对癌细胞具有选择性细胞毒性的前药(同时对外周血单核细胞[PBMC]、星形胶质细胞、神经元和肝细胞无害)。