title: Breast cancer metastasis suppressor 1 regulates hepatocellular carcinoma cell apoptosis via suppressing osteopontin expression.
abstract: Breast cancer metastasis suppressor 1 (BRMS1) was originally identified as an active metastasis suppressor in human breast cancer. Loss of BRMS1 expression correlates with tumor progression, and BRMS1 suppresses several steps required for tumor metastasis. However, the role of BRMS1 in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that the expression level of BRMS1 was significantly down-regulated in HCC tissues. Expression of BRMS1 in SK-Hep1 cells did not affect cell growth under normal culture conditions, but sensitized cells to apoptosis induced by serum deprivation or anoikis. Consistently, knockdown of endogenous BRMS1 expression in Hep3B cells suppressed cell apoptosis. We identified that BRMS1 suppresses osteopontin (OPN) expression in HCC cells and that there is a negative correlation between BRMS1 and OPN mRNA expression in HCC tissues. Moreover, knockdown of endogenous OPN expression reversed the anti-apoptosis effect achieved by knockdown of BRMS1. Taken together, our results show that BRMS1 sensitizes HCC cells to apoptosis through suppressing OPN expression, suggesting a potential role of BRMS1 in regulating HCC apoptosis and metastasis.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wu
authors.forename: Wenjun
authors.initials: W
authors.lastname: Jiang
authors.forename: Yingming
authors.initials: Y
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Hexige
authors.initials: H
authors.lastname: Saiyin
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Qiao
authors.forename: Xinyu
authors.initials: X
authors.lastname: Mei
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.forename: Xiao
authors.initials: X
authors.lastname: Fang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Huiling
authors.initials: H
authors.lastname: Lou
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Wu
authors.forename: Shouyi
authors.initials: S
authors.lastname: Qiao
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins
chemical_list: C410024:BRMS1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D053495:Osteopontin