Abstract
MiR-589-5p could promote liver cancer, but the specific mechanisms are largely unknown. This study examined the role and mechanisms of miR-589-5p in liver cancer. The expressions of miR-589-5p, METTL3 and m6A in liver cancers were determined by RT-qPCR. The relationship between miR-589-5p and METTL3-mediated m6A methylation was examined by m6A RNA immunoprecipitation. After transfection, the viability, migration, invasion and expressions of METTL3 and miR-589-5p in liver cancer cells were detected by CCK-8, wound-healing, transwell and RT-qPCR. After the xenograft tumour was established in mice, the tumour volume was determined and the expressions of METTL3, miR-589-5p, MMP-2, TIMP-2, E-cadherin, N-cadherin and Vimentin in tumour tissue were detected by RT-qPCR and Western blotting. In vitro study showed that miR-589-5p and METTL3 were highly expressed in liver cancer. METTL3 was positively correlated with miR-589-5p. METTL3 up-regulated the expression of miR-589-5p and promoted the maturation of miR-589-5p. Overexpressed miR-589-5p and METTL3 promoted the viability, migration and invasion of liver cancer cells, while the effects of silencing miR-589-5p and METTL3 on the cells were the opposite. The effects of METTL3 overexpression and silencing were reversed by miR-589-5p inhibitor and mimic, respectively. In vivo study showed that METLL3 silencing inhibited the growth of xenograft tumour and the expressions of METTL3, MMP-2, N-cadherin and Vimentin, promoted the expressions of TIMP-2 and E-cadherin, while miR-589-5p mimic caused the opposite results and further reversed the effects of METLL3 silencing. In summary, this study found that METTL3-mediated maturation of miR-589-5p promoted the malignant development of liver cancer.
Keywords:
METTL3; liver cancer; m6A methylation; miR-589-5p; pri-miR-589.