Abstract
Non-small cell lung cancer (NSCLC) is one of the major causes of morbidity and mortality worldwide. We aimed to investigate the role of N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) regulating microRNA-1246 (miR-1246) in the progression of NSCLC by targeting paternally expressed gene 3 (PEG3). METTL3, miR-1246, and PEG3 expression in tissues was assessed, and the predictive role of METTL3 in prognosis of patients with NSCLC was detected. NSCLC cells were relatively treated with altered expression of METTL3, miR-1246, or PEG3 to measure their roles in the proliferation, migration, invasion, apoptosis, and in vivo growth of the NSCLC cells. The RNA m6A level was determined, and the targeting relationship between miR-1246 and PEG3 was confirmed. Our results revealed that METTL3 and miR-1246 were upregulated, whereas PEG3 was downregulated in NSCLC tissues. METTL3 knockdown or PEG3 overexpression in NSCLC cells suppressed malignant behaviors of NSCLC cells. METTL3 affected the m6A modification of miR-1246, thus upregulating miR-1246 and miR-1246-targeted PEG3. The elevation of PEG3 reversed the effects of miR-1246 upregulation on NSCLC cells. This study revealed that m6A methyltransferase METTL3 affects the m6A modification of miR-1246, thus upregulating miR-1246 to promote NSCLC progression by inhibiting PEG3.