MiR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B

Abstract

miR-29s (including miR-29a–c) have been confirmed to be effective tumor suppressors for a variety of malignant tumors including glioblastoma. Promoter hypermethylation resulting from DNMT3A and 3B overexpression is an important epigenetic mechanism for tumor suppressive gene silencing. Bioinformatics predicts both DNMT3A and 3B are targets of miR-29s, but the anti-glioblastoma effects of miR-29s induced DNMT3A/3B downregulation deserve further investigation. We herein demonstrated that miR-29s effectively blocked DNMT3A and 3B expression by degrading their mRNAs in U87MG glioblastoma cell line. Exogenous miR-29s substantially inhibited the proliferation, migration and invasion of U87MG cells, and promoted their apoptosis. These effects could be perfectly mimicked by a small interfering RNA against DNMT3A and 3B, and partially compromised by DNMT3A/3B expression plasmids co-transfection, suggesting that miR-29s exerted the above tumor suppressive effects at least partly by silencing DNMT3A/3B. These findings provide a rationale for miR-29s based therapeutic strategies against glioblastoma.