The positive feedback between ACSL4 expression and O-GlcNAcylation contributes to the growth and survival of hepatocellular carcinoma
Jiachen Wang, Zhao Wang, Jiaxiang Yuan, Jiaxiang Wang, Xinsheng Shen
Abstract
tumour formation assays were performed to detect cell proliferation, apoptosis and tumorigenesis. IP technology was used to evaluate the relationship between ACSL4 and O-GlcNAc. ACSL4, GLUT1 and O-GlcNAc levels were elevated in HCC tissues and predicted poor prognosis in HCC patients. ACSL4 overexpression significantly promoted cell proliferation and tumorigenesis and inhibited cell apoptosis, whereas these effects were all obviously impaired when mTOR signalling was repressed or GLUT1 was downregulated. ACSL4 could be O-GlcNAcylated, and silencing of ACSL4 abolished the effects of O-GlcNAcylation on cell growth promotion and apoptosis inhibition. Collectively, this study demonstrates that ACSL4 contributes to the growth and survival of HCC by enhancing GLUT1-mediated O-GlcNAcylation. In turn, O-GlcNAcylation promotes HCC growth partially by increasing ACSL4 expression.