Modomics - A Database of RNA Modifications

Published on Aug. 27, 2019 in Biochem Biophys Res Commun volume 516(3).

PubMed ID: 31253399

DOI: 10.1016/j.bbrc.2019.06.128


Osteosarcoma(OS) is the most common and aggressive malignant bone sarcoma,whichoccurs in rapidly growing bones in children and adolescents. However, the underlyingmolecular mechanisms of OS development have not been fully illustrated.N6-Methyladenosine (m6A) is the most prevalent internal chemical modification ofmRNAs, which is involved in many pathological processes in cancer development.However, its role and regulatory mechanism in OS remain unknown. In this study, weaimed to investigate the roles of m6A and its methyltransferase METTL3 in OSdevelopment. The results showed that m6A level for RNA methylation and theexpression level of METTL3 were up-regulated in human OS tissues and OS cell lines.Functionally, lentivirus-mediated METTL3 silence in HOS and SAOS-2 cells inhibitedthe cell proliferation, migration and invasion ability. Further mechanism analysissuggested that METTL3 silence decreased the m6A methylation and total mRNA level oflymphoid enhancer-binding factor 1 (LEF1), followed by inhibited the activity ofWnt/β-catenin signaling pathway. Moreover, LEF1 over-expression abrogates therepressive effects of METTL3 silence on the proliferation, migration and invasionabilities of OS cells. Together, these results revealed that the m6Amethyltransferase METTL3 promotes osteosarcoma cell progression by regulating them6A level of LEF1 and activating Wnt/β-catenin signaling pathway.CI - Copyright © 2019 Elsevier Inc. All rights reserved.