breast cancer metastasis suppressor 1 regulates hepatocellular carcinoma cell apoptosis via suppressing osteopontin expression乳腺癌转移抑制基因1通过抑制骨桥蛋白表达调控肝癌细胞凋亡.pdf

Breast Cancer Metastasis Suppressor 1 Regulates Hepatocellular Carcinoma Cell Apoptosis via Suppressing Osteopontin Expression Yanhua Wu., Wenjun Jiang., Yingming Wang, Jun Wu, Hexige Saiyin, Xiaojing Qiao, Xinyu Mei, Bin Guo, Xiao Fang, Lu Zhang, Huiling Lou, Chaoqun Wu, Shouyi Qiao* State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China 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. Citation: Wu Y, Jiang W, Wang Y, Wu J, Saiyin H, et al. (2012) Breast Cancer Metastasis Suppressor 1 Regulates Hepatocellular Carcinoma Cell Apoptosis via Suppressing Osteopontin Expression. PLoS ONE 7(8): e