title: NS5ABP37 inhibits liver cancer by impeding lipogenesis and cholesterogenesis.
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.
authors.affiliation: Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.
authors.forename: Shenghu
authors.initials: S
authors.lastname: Feng
authors.affiliation: Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Han
authors.affiliation: Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Lu
authors.affiliation: Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.|Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002784:Cholesterol / Q000096:biosynthesis*; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress; D005353:Fibronectins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050155:Lipogenesis; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: C543006:FNDC3B protein, human; D005353:Fibronectins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051779:Sterol Regulatory Element Binding Proteins; D014280:Triglycerides; D002784:Cholesterol; D053148:Caspase 3; D053179:Caspase 7
keywords: ER stress; NS5ABP37; lipid metabolism; liver cancer; oxidative stress