NS5ABP37 inhibits liver cancer by impeding lipogenesis and cholesterogenesis. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Feng, Shenghu; Han, Ming; Zhou, Li; Wang, Qi; Li, Zhongshu; Li, Yaru; Lu, Hongping; Liu, Ting; Ma, Yanhua; Liu, Shunai; Cheng, Jun
• Is Part Of: Cancer science. Volume 108:Issue 1(2017)
• Page Start: 12
• Page End: 22
• Publication Date: 2017-01
• Subjects: ER stress -- lipid metabolism -- liver cancer -- NS5ABP37 -- oxidative stress; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13117
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : The molecular mechanism underlying non‐alcoholic fatty liver disease progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining results showed that NS5ABP37 protein, which is in a state of lower expression in tumor tissues, decreased with increasing degree of HCC malignancy. Two cell models, HepG2 and L02, were used to analyze the mechanism between NS5ABP37 and HCC. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1 /S cell cycle arrest, and induced apoptosis by increasing caspase‐3/7 activity and cleaved caspase‐3 levels. In addition, NS5ABP37 overexpression resulted in decreased intracellular triglyceride and total cholesterol contents, with level reduction in sterol regulatory element‐binding proteins (SREBPs) and downstream effectors. Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by reducing their respective promoters. Finally, reactive oxygen species levels and endoplasmic reticulum stress were both induced by NS5ABP37 overexpression. These findings together indicate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP‐dependent lipogenesis and cholesterogenesis in HepG2 and L02 cells and inducing oxidative stress and endoplasmic reticulum stress. Abstract : We showed that NS5ABP37 reduced triglyceride and cholesterol levels in HepG2 cells via regulating the expression of SREBPs. We demonstrated that the regulation of NS5ABP37 on lipid metabolism may induce cell apoptosis and inhibit cell proliferation. We illustrated that NS5ABP37 induced oxidative stress and ER stress, which proved to be potential element in both lipid metabolism and cancer cell growth.