BIRC6 promotes hepatocellular carcinogenesis: Interaction of BIRC6 with p53 facilitating p53 degradation

Wenqing Tang, Ruyi Xue, Shuqiang Weng, Jian Wu, Ying Fang, Yi Wang, Lingling Ji, Tingting Hu, Taotao Liu, Xiaowu Huang, She Chen, Xizhong Shen, Si Zhang, Ling Dong

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The genes that encode inhibitor of apoptosis proteins (IAPs) are frequently overexpressed in human cancers. However, the expression pattern and clinical significance of BIRC6, a member of IAPs, in hepatocellular carcinoma (HCC) remains unclear. Here we investigated the role of BIRC6 in hepatocellular carcinogenesis. We used immunoblot and immunochemical analyses to determine the levels of BIRC6 in 7 hepatoma cell lines and 160 HCC specimens. We evaluated the proognostic value of BIRC6 expression and its association with clinical parameters. A lentivirus-mediated silencing method was used to knockdown BIRC6, and the biological consequences of BIRC6 silencing in three hepatoma cell lines were investigated in vitro and in vivo. We found that BIRC6 overexpression was significantly correlated with serum ALT level and HCC vascular invasion. Patients with positive BIRC6 expression in tumor tissue had a poor survival and a high rate of recurrence. BIRC6 knockdown remarkably suppressed cell proliferation, caused G1/S arrest and sensitized hepatoma cells to sorafenib-induced apoptosis in hepatoma cells, which was partly reversed by RNA interference targeting p53. The mechanistic study revealed that BIRC6 interacted with p53 and facilitated its degradation. The in vivo study showed that BIRC6 knockdown inhibited xenograft tumor growth and increased the sensitivity of tumor cells to sorafenib in nude mice. Taken together, these findings demonstate that BIRC6 overexpression in HCC specimens is indicative of poor prognosis and that its interaction with p53 facilitates the degradation of p53, leading to carcinogenesis and an anti-apoptotic status.

Original languageEnglish (US)
Pages (from-to)E475-E487
JournalInternational Journal of Cancer
Issue number6
StatePublished - Mar 15 2015
Externally publishedYes


  • Apoptosis
  • G1/S arrest
  • Growth inhibition
  • Tumorigenesis
  • Ubiquitination

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)


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