NS5ABP37 inhibits liver cancer by impeding lipogenesis and cholesterogenesis

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• 作者：Shenghu Feng ; Ming Han ; Li Zhou ; Qi Wang ; Zhongshu Li ; Yaru Li ; Hongping Lu ; Ting Liu ; Yanhua Ma ; Shunai Liu and Jun Cheng
• 刊名：Cancer Science
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：108
• 期：1
• 页码：12-22
• 全文大小：1935K
• ISSN：1349-7006

文摘

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.