Effects Of METTL14 On Proliferation,Migration And Epithelial-Mesenchymal Transition Of Non-Small Cell Lung Cancer Cells

Objective Non-small cell lung cancer(NSCLC)is the leading cause of cancer-related deaths worldwide,and its 5-year survival rate is very low.Thus,it is important to explore the underlying pathogenesis of NSCLC for the treatment of NSCLC.Recently,multiple evidences have demonstrated that N6-methyladenosine(m6A)plays important roles in various cancers.However,Methyltransferase-like 14(METTL14),serving as the main component of m6A complex,has less been reported to engage in NSCLC development.The target of this study was to investigate the role of METTL14 in NSCLC and the underlying mechanisms.Methods(1)After downloading NSCLC data from the Cancer Genome Atlas(TCGA)database and the Gene Expression Omnibus(GEO)database,gene expression profiles of m6A methylation regulators were obtained.R was used to evaluate the expression of METTL14 in NSCLC and analyze the correlations between the expression levels of METTL14 and tumor stage.Univariate COX analyses were performed to analyze 13 m6A methylation regulators to obtain the risk genes associated with NSCLC.(2)The protein expression of METTL14 in NSCLC cells was detected by Western Blot.(3)Silencing of METTL14 in A549 cells and SK-MES-1 cells,and the proliferation and clonality of cells was detected by Western Blot.(4)Silencing of METTL14 in A549 cells and SK-MES-1 cells,and the protein expression of E-cadherin,N-cadherin,and EMT-related transcription factor was detected by Western Blot.(5)Silencing of METTL14 in A549 cells and SK-MES-1 cells,and the migration of cells was detected by Transwell assays.(6)Silencing of METTL14 in A549 cells,the protein expression levels of p-AKT and p-GSK3β was detected by Western Blot.Results(1)METTL14 was highly expressed in NSCLC tissues,and its expression was high in stage I,II,Ⅲ,and IV NSCLC patients,METTL14 was identified as the risk gene for NSCLC.(2)METTL14 was highly expressed in NSCLC cells compared with normal human bronchial epithelial cells(16HBE).(3)METTL14 knockdown inhibits NSCLC cells proliferation and clonality.(4)METTL14 knockdown in NSCLC cells can reverse its EMT phenotype and reduce the cell migration.(5)METTL14 knockdown in NSCLC cells may inhibit its EMT processes via reducing the expression levels of Twist,p-AKT.Conclusion METTL14 was highly expressed in NSCLC,METTL14 knockdown inhibited the proliferation,migration and epithelial-mesenchymal transition of NSCLC cells,which provides a potential target for the treatment of NSCLC.