Mechanism of N6-methyladenosine(m6A)transferase METTL3 and m6A reg-ulation of LINC01465 in the proliferation and metastasis of hepatocellular car-cinoma
Objective To investigate the mechanism of methyltransferase like 3(METTL3)in hepatocellular carcinoma cells to regulate the level of m6 A,affect the expression of long-chain non-coding(lncRNA)LINC01465,and promote the proliferation and metastasis of hepatocellular carcinoma cells.Methods The Canc-er Genome Atlas(TCGA)database was used to analyze the expression differences of METTL3 in hepatocellular carcinoma tissues and normal liver tissues and explain its relationship with patients'prognosis;the expression of METTL3 in cells and tissues was verified by western blot and RT-qPCR analyses;the levels of m6A were verified by the m6A colorimetric assay in hepatocellular carcinoma cells and normal hepatocytes;and after the knock-down of METTL3,the CCK-8,clone formation,Transwell migration,and invasion assays was used to study the regulatory role of METTL3 on the proliferation and metastasis of hepatocellular carcinoma;transcriptome RNA m6A methylation sequencing was performed to determine LINC01465,the downstream regulatory gene of MET-TL3.RT-qPCR was performed to verify the expression of LINC01465 after silencing of METTL3 and the expres-sion level of LINC01465 in hepatocellular carcinoma.Results METTL3 was significantly highly expressed in hep-atocellular carcinoma tissues and cells and was associated with poorer prognosis of patients;highly expressed METTL3 promoted the proliferation,migration and invasion of HCC cells;METTL3 affected the m6A level of LINC01465 and its expression,promoting the developmental process of hepatocellular carcinoma.Conclusion METTL3 can affect the expression level of LINC01465 in an m6A-dependent manner to promote the proliferation and metastasis ability of hepatocellular carcinoma cells,suggesting that METTL3 may become a target marker for the prognosis and treatment of hepatocellular carcinoma.
methyltransferase like 3N6-methyladenosine methylationLINC01465hepatocellular carcinoma
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