LncRNA NUTM2A-AS1 Regulates The Viability And Apoptosis Of Lung Adenocarcinoma Cells Through The MiR-590-5p/METTL3 Axis

Objective:Lung cancer is the leading cause of cancer-related deaths worldwide,of which 38.5%are lung adenocarcinomas（LUAD）.LUAD,characterized by high somatic mutation rate and genome rearrangement rate,is prone to early metastasis,which average 5-year survival rate is<20%.With the deepening of research,more and more lncRNA molecules have been found to be abnormally expressed in lung cancer.The up-regulated expression of NUTM2A-AS1 in LUAD and the hypomethylation of its promoter region may promote its carcinogenic effect.However,The underlying molecular mechanism is still unclear.Further exploration of the mechanism of action of NUTM2A-AS1 in LUAD is of great significance for the identification of new LUAD biomarkers and effective targeted therapies.Method:The bioinformatics analysis and dual luciferase reporter gene detection were used to clarify the relationship between miR-590-5p and NUTM2A-AS1.The expression of NUTM2A-AS1 and miR-590-5p in LUAD cells with or without the treatment of si-NUTM2A-AS1 and miR-590-5p inhibitor were detected by RT-qPCR.The proliferation ability and apoptosis level of NCI-H23 cells with the treatment of si-NUTM2A-AS 1 and miR-590-5p inhibitor were analysed by MTT detection and flow cytometry.The bioinformatics analysis and dual luciferase reporter gene detection were used to clarify the targeting relationship between miR-590-5p and METL3.RT-qPCR and Western blotting were used to detect the expression of METL3 in LUAD cells.The proliferation and apoptosis of NCI-H23 cells after overexpression of miR-590-5p and METTL3 were detected by MTT detection and flow cytometry.Results:MiR-590-5p directly targets NUTM2A-AS1 in lung adenocarcinoma,and both of them are overexpressed in LUAD cell lines compared to normal lung epithelial cells.Knockdown of NUTM2A-AS1 can inhibit the proliferation of NCI-H23 cells and promote cell apoptosis,which can be reversed by further treatment with miR-590-5p inhibitors.Deeply prediction of the downstream target genes of miR-590-5p showed that METTL3 is the direct target of miR-590-5p.RT-qPCR and Western blot results showed that the expression level of METL3 in LUAD cell lines were significantly up-regulated.After overexpression of miR-590-5p and METTL3,the expression of miR-590-5p and METTL3 in NCI-H23 cells was markably increased,which inhibited the cell proliferation ability and induced cell apoptosis.Conclusions:The long non-coding RNA NUTM2A-AS1 is dysregulated in LUAD,and knockdown of NUTM2A-AS1 can inhibit the viability of LUAD cells and induce cell apoptosis by up-regulating the expression of miR-590-5p.In addition,METTL3 has been identified as the direct target of miR-590-5p,which inhibits the viability of NCI-H23 cells and induces apoptosis by down-regulating METTL3.Therefore,the lncRNA NUTM2A-AS1/miR-590-5p/METTL3 axis may be a new molecular mechanism involved in the progression of LUAD and a potential therapeutic target for LUAD therapy.