FTO-Mediated N6-Methyladenosine Modification of KLF3 Promotes Osteosarcoma Progression

Abstract

N6-methyladenosine (m6A) methylation is the most common and abundant methylation modification of eukaryotic mRNAs, which is involved in tumor initiation and progression. This study aims to explore the functional role and regulatory mechanism of FTO in osteosarcoma progression. In this study, we detected the expressions of KLF3 in OS cells and tissues by qRT-PCR and western blot, and found that the mRNA and protein expressions of KLF3 were increased in OS cells and tissues and significantly related to tumor size, metastasis, and TNM stage and poor prognosis of OS patients. FTO promoted the proliferation and invasion and suppressed apoptosis of OS cells through CCK-8, Transwell and apoptosis assays. Further mechanism dissection revealed that FTO and YTHDF2 enforced the decay of KLF3 mRNAs and decreased its expression. Knockdown of FTO led to elevate m6A and mRNA levels. FTO-mediated m6A modification regulated KLF3 expression in the YTHDF2-dependent manner. Moreover, KLF3 overexpression abrogated FTO-induced oncogenic effects on the proliferation and invasion of OS cells. Overall, our findings showed that FTO-mediated m6A modification of KLF3 promoted OS progression, which may provide a therapeutic target for osteosarcoma.