Scinderin is a novel transcriptional target of BRMS1 involved in regulation of hepatocellular carcinoma cell apoptosis.

ABSTRACT

Tumor metastasis suppressor factor BRMS1 can regulate the metastasis of breast cancer and other tumors. Here we report scinderin (SCIN) as a novel transcriptional target of BRMS1. SCIN protein belongs to the cytoskeletal gelsolin protein superfamily and its involvement in tumorigenesis remains largely illusive. An inverse correlation between the expression levels of BRMS1 and SCIN was observed in hepatocellular carcinoma (HCC) cells and tissues. On the molecular level, BRMS1 binds to SCIN promoter and exerts a suppressive role in regulating SCIN transcription. FACS analysis and caspase 9 immunoblot reveal that knockdown of SCIN expression can sensitize HCC cells to chemotherapeutic drugs, leading to suppression of tumor growth in vivo. Consistently, overexpression of SCIN protects cells from apoptotic death, contributing to increased xenografted HCC cell growth. In summary, our study reveals SCIN as a functional apoptosis regulator as well as a novel target of BRMS1 during HCC tumorigenesis. Inhibition of SCIN might bring a potential cancer therapy approach.