Background Prognosis of hepatocellular carcinoma (HCC) remains poor due to high recurrence rate and ineffective treatment options, highlighting the need to better understand the mechanism of recurrence and metastasis in HCC. Methods We first collected messenger RNA (mRNA) expression data from 442 cases of HCC patients from The Cancer Genome Atlas (TCGA) database as well as 251 HCC patients from Zhongshan Hospital during 2009 and 2010 to analyze the expression pattern from tissue microarray (TMA) of baculoviral IAP repeat containing 3 (BIRC3). Then, we used BIRC3 gain-of-function (overexpression) and loss-of-function (knockdown) studies to examine the effect of BIRC3 on HCC cell proliferation and invasion. In addition, we also investigated the undying mechanism by which BIRC3 contributes to HCC tumor progression. Functionally, we also used a BIRC3-specific inhibitor AT-406 in HCC xenograft model to explore the potential therapeutic benefit of targeting BIRC3 in liver cancer. Results BIRC3 serves as a novel prognostic indicator for HCC patients undergoing curative resection. BIRC3 promotes HCC epithelial-mesenchymal transition (EMT), cell migration, and metastasis via upregulating MAP3K7, therefore, inducing ERK1/2 phosphorylation. The specific BIRC3 inhibitor AT-406 can inhibit HCC cell proliferation and reduce pulmonary metastases. Conclusion BIRC3 induces tumor proliferation and metastasis in vitro and in vivo. BIRC3 may serve as a novel therapeutic target for liver cancer.
[1]Fudan Univ, Liver Canc Inst, Zhongshan Hosp, Dept Liver Surg & Transplantat, 136 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China;
[2]Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai, Peoples R China;
[3]Fudan Univ, Liver Canc Inst, Zhongshan Hosp, Lab Med Dept, Shanghai, Peoples R China;
[4]Fudan Univ, State Key Lab Genet Engn, Shanghai, Peoples R China;
[5]Fudan Univ, Shanghai Key Lab Organ Transplantat, Zhongshan Hosp, Shanghai, Peoples R China;
[6]Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China
(8.0+极速模式)