title: Cold-inducible RNA-binding protein promotes the development of liver cancer.
abstract: Most hepatocellular carcinomas (HCCs) develop in the context of chronic liver inflammation. Oxidative stress is thought to play a major role in the pathogenesis of HCC development. In this study, we examined whether cold-inducible RNA-binding protein (Cirp) controls reactive oxygen species (ROS) accumulation and development of HCC by using murine models of hepatocarcinogenesis and human liver samples. Cirp expression, ROS accumulation, and CD133 expression were increased in the liver of tumor-harboring mice. Cirp deficiency reduced production of interleukin-1β and interleukin-6 in Kupffer cells, ROS accumulation, and CD133 expression, leading to attenuated hepatocarcinogenesis. Thioacetamide treatment enhanced hepatic expression of CD133 and phosphorylated signal transducer and activator of transcription 3 (STAT3), which was prevented by treatment with the antioxidant butylated hydroxyanisole. Intriguingly, the risk of human HCC recurrence is positively correlated with Cirp expression in liver. Cirp appears to play a critical carcinogenic function and its expression might be a useful biomarker for HCC risk prediction.
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Norihisa
authors.initials: N
authors.lastname: Yada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Arizumi
authors.forename: Satoru
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Ueshima
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nishida
authors.forename: Jun
authors.initials: J
authors.lastname: Fujita
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000975:Antioxidants / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D010455:Peptides; D010766:Phosphorylation / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013853:Thioacetamide / Q000494:pharmacology; D016707:Tissue Fixation
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000975:Antioxidants; C106176:Cirbp protein, mouse; D006023:Glycoproteins; D053583:Interleukin-1beta; D015850:Interleukin-6; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D055748:SOXB1 Transcription Factors; D050796:STAT3 Transcription Factor; C527783:Sox2 protein, mouse; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse; D013853:Thioacetamide; D002083:Butylated Hydroxyanisole
keywords: CD133; HCC; ROS; recurrence; stem cell