Retraction.

Abstract

Increasing evidence have demonstrated that methyltransferase-like 3 (METTL3) plays an oncogenic role in the development of human hepatocellular carcinoma (HCC), however, the underlying mechanisms still remain largely unexplored. We investigated the effect of METTL3/microRNA-873-5p (miR-873-5p)/suppressor with the morphological effect on genitalia 1 (SMG1) axis on the progression of HCC. Bioinformatics databases were used to predict new HCC-related pathways. HCC cells were then selected for determining the expression of METTL3, miR-873-5p, and SMG1. Dual luciferase reporter gene assay, co-immunoprecipitation and RNA binding protein immunoprecipitation were employed to explore the relationship between miR-873-5p and SMG1, binding between METTL3 and DiGeorge critical region 8 (DGCR8), and the enrichment of DGCR8 and N6-methyladenosine (m6A) on pri-miR-873-5p, respectively. Additionally, the effect of METTL3 on the malignant phenotypes of HCC cells as well as the tumorigenicity of transfected cells were examined with gain-and-loss-of-function experiments. Bioinformatics databases suggested that METTL3 increased the expression of miR-873-5p in an m6A-dependent way, thereby suppressing the expression of SMG1 to promote the development of HCC. In HCC cells, miR-873-5p and METTL3 were highly expressed, while SMG1 was under-expressed. miR-873-5p promoted the malignant phenotypes in HCC cells by the negative regulation of SMG1. METTL3 promoted the m6A modification of pri-miR-873-5p, contributing to an increased expression of miR-873-5p. METTL3 also accelerated tumor formation in nude mice by down-regulating the expression of SMG1. Our study revealed that METTL3 inhibited the expression of SMG1 through m6A modification-mediated miR-873-5p up-regulation, thus playing an oncogenic role in HCC.