FAM83D promotes the proliferation and migration of hepatocellular carcinoma cells by inhibiting the FBXW7/MCL1 pathway

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant tumors and has a poor 5-year survival rate. Family with sequence similarity 83, member D (FAM83D) is characterized as an oncogenic gene related to cell proliferation in many tumors, but the role and underlying mechanism of FAM83D in the development of HCC are still unclear. METHODS: FAM83D expression profiles and clinicopathological data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Additionally, 2 data sets from the Gene Expression Omnibus (GEO) database were used to further validate the FAM83D profile in HCC. We then downregulated the expression of FAM83D in HCC cells transfected with FAM83D small-interfering ribonucleic acid (siRNA) and upregulating its expression by FAM83D-overexpression transfection for further in vitro studies. RESULTS: TCGA and the GEO databases showed that FAM83D was significantly more upregulated in tumor tissues than non-tumor tissues. The high expression of FAM83D in HCC is associated with poor prognostic clinical factors. The knockdown of FAM83D in SNU449 and HUH7 cells in vitro impaired cell proliferation and migration, and promoted apoptosis, while the overexpression of FAM83D in BEL7402 cells had the opposite effect. Further, combined transfection with FBXW7 siRNA or MCL1-overexpression reversed the role of FAM83D knockdown on cell proliferation, migration, and apoptosis in vitro, while FBXW7 expression was negatively correlated with both the FAM83D and MCL1 levels in TCGA-LIHC patients. CONCLUSIONS: FAM83D played a significant role in HCC progression by enhancing cell proliferation and migration and inhibiting apoptosis, which may have been caused by the inhibition of the FBXW7/MCL1 signaling pathway. Thus, FAM83D may be a promising therapeutic target for HCC.