We also investigated whether BIRC6 affected therapeutic response
to sorafenib. Furthermore, we explored whether there was direct interaction Tyrosine Kinase Inhibitor Library in vivo between BIRC6 and p53 accounting for the function of BIRC6. Methods: 160 tissue samples of HCC patients with liver resection were evaluated for BIRC6 expression via immunohistochemistry. The correlation of BIRC6 expression in the tumor tissue with clinicopathologic features was analyzed by chi-square test, and the prognosis patterns were further examined by Kaplan–Meier analysis and Cox regression analysis. The biological effects of BIRC6 on cell proliferation, cell cycle, and apoptosis as well as effect of BIRC6-knockdown on function of sorafenib were
examined by BIRC6 silencing in two epithelial cell lines of HCC and tumor-bearing mice model. The correlation between BIRC6 and p53 was studied by immunofluorescence, immunoprecipitation and ubiquitination experiment. Results: Up-regulated expression of cytoplasmic/nuclear BIRC6 protein was observed in the majority of the tumor tissues when compared with the adjacent non-tumorous liver tissues. Further analysis showed that overexpression of BIRC6 expression in the tumor tissues was associated with ALT, vascular invasion and TNM stage. Patients with BIRC6-positive expression in tumor tissue had poor prognosis of survival and recurrence. Knockdown of BIRC6 could suppress carcinogenesis, promote apoptosis and enhance the therapeutic effect of sorafenib both in vitro and vivo. selleck compound As an upstream regulator of p53 in signal pathway of HCC, BIRC6 could directly degrade p53 by ubiquitination. Conclusion: BIRC6 promotes carcinogenesis and inhibits apoptosis in HCC through regulating the degradation of p53. 上海皓元医药股份有限公司 There exist synergistic effects on depressing tumorgenesis between suppression of the BIRC6 function and sorafenib. BIRC6 could be a promising target of novel gene therapy and a useful marker for assessing prognosis
of HCC. Key Word(s): 1. BIRC6; 2. liver cancer; 3. prognosis; 4. p53; Presenting Author: BEIFANG NING Additional Authors: WENPING XU, CHUAN YIN, JIANXIONG WANG, XIN ZHANG, WEIFEN XIE Corresponding Author: WEIFEN XIE Affiliations: Shanghai Changzheng Hospital; Department of Gastroenterology, Changzheng Hospital Objective: Hepatocyte nuclear factor 4α (HNF4α) plays a key role in hepatocyte differentiation and hepatic function maintenance. However, the function of HNF4α in hepatocellular carcinoma (HCC) remains obscure. Herein, we clarified the role of HNF4α in HCC progression and the underlying mechanism. Methods: The recombinant adenoviruses carrying HNF4α gene were injected into HCC Xenograft mice through tail vein. Expression of epithelial-mesenchymal transition (EMT) and NF-кB related genes were detected by Real-time PCR or immunohistochemistry.