m6A methyltransferase like 3 upregulates microRNA-1246 to promote occurrence and progression of non-small cell lung cancer via targeting paternally-expressed gene 3

Abstract Non-small cell lung cancer (NSCLC) is one of the major causes of morbidity and mortality worldwide. We aim to investigate the role of m6A methyltransferase like 3 (METTL3) regulating microRNA-1246 (miR-1246) in the progression of non-small cell lung cancer (NSCLC) by targeting paternally-expressed gene 3 (PEG3). METTL3, miR-1246 and PEG3 expression in tissues were 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 the NSCLC progression by inhibiting PEG3.