Investigated the Role of Mir-200 Family in the Prognostic and Therapeutic of Hcc and Dissected the Possible Mechanism

Hepatocellular carcinoma (HCC) is a high prevalence malignancy in Taiwan. There are several difficulties in the treatment of HCC. The prevalence of hepatitis B virus infection, poor detection rate of current examination method, low proportion of HCC patients feasible for curative surgery, and no effective chemotherapy agents are four main obstacles for HCC treatment. Recent studies have been shown miRNA may be the potential therapeutic targets for cancers. In order to figure out the miRNA target for HCC, we performed miRNA array analysis in three different HCC cells (HepG2, HepJ5, and skHep-1). We found miR-200a and miR-200b are correlated with the differentiation levels of HCC cells. Hypoxia stress is a common phenomenon in human solid tumors and plays a critical role in tumor progression. Hypoxia has been considered as an inducer of EMT-like process in diverse human solid malignancies such as HCC. We found overexpressed miR-200a or miR-200b didn’t influence the growth activity on HCC cells. However, the survival rate in miR-200a or miR-200b overexpressed HCC cells was increased dramatically. This indicate that miR-200 family may play the specific role in HCC under stress condition. In this study, we plan to dissect the role of miR-200a or miR200b in HCC progression and therapeutic responses under normoxia and hypoxia condition. We included the specific aims as followed. Aim 1: To investigate the roles of miR-200a and miR-200b in HCC under normoxic /hypoxic conditions；Aim 2: To investigate the roles of miR-200a and miR-200b in hypoxic neo-angiogenesis, metastasis and the dissection of the molecular mechanism；Aim 3: To explore the role of miR-200a and miR-200b in chemoresistance and radioresistance。We believe this study may give the novel information for clinical therapy on HCC.