Transcriptional Regulation of Human Osteopontin in Hepatocellular Cacinoma Cells

Abstract: Osteopontin (OPN) is a secreted glycophosphoprotein which is important in cell adhesion，migration， body immune， etc. Recent studies recognized the essential role of OPN in carcinogenesis and tumor metastasis through regulating extracellular cell matrix (ECM) degradation and remodeling. OPN is significantly up-regulated in multiple cancers including hepatocellular carcinoma (HCC)， and is relevant with the malignancy.However， the molecular mechanism of OPN regulation remains largely illusive. In our study， in order to investigate the regulation mechanism of OPN gene SPP1 in hepatocellular carcinoma， the full-length promoter (pSPP1) was cloned.Deletion and point mutation analysis demonstrated that –24~–17 region is essential for the transcriptional activity of pSPP1. Overexpression of AP-1 factor subunit c-jun， but not c-fos， can significantly enhance the transcriptional activity， and EMSA assay proved the direct binding of c-jun to pSPP1. Moreover， overexpression of c-jun can effectively induce endogenous OPN expression， which is demonstrated by both Western blot and qRT-PCR assay.Taken together， our findings recognize AP-1 factor as a key mechanism of OPN regulation in HCC cell， which brings new insights into HCC diagnosis and gene therapy.

CSTR: 32200.14.cjcb.2015.08.0003