Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital of Fudan University, Shanghai, China.
Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
J Cell Biochem. 2019 Apr;120(4):6035-6045. doi: 10.1002/jcb.27890. Epub 2018 Oct 28.
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.
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.
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.
BIRC3 induces tumor proliferation and metastasis in vitro and in vivo. BIRC3 may serve as a novel therapeutic target for liver cancer.
由于肝癌（HCC）的高复发率和治疗选择有限，其预后仍然较差，这凸显了我们需要更好地理解 HCC 复发和转移的机制。
我们首先从癌症基因组图谱（TCGA）数据库中收集了 442 例 HCC 患者的信使 RNA（mRNA）表达数据，以及 2009 年至 2010 年中山医院的 251 例 HCC 患者的组织微阵列（TMA）数据，以分析杆状病毒 IAP 重复序列 3（BIRC3）的表达模式。然后，我们使用 BIRC3 功能获得（过表达）和功能丧失（敲低）研究来检查 BIRC3 对 HCC 细胞增殖和侵袭的影响。此外，我们还研究了 BIRC3 促进 HCC 肿瘤进展的不灭机制。在功能上，我们还在 HCC 异种移植模型中使用了 BIRC3 特异性抑制剂 AT-406，以探索靶向 BIRC3 在肝癌中的潜在治疗益处。
BIRC3 是接受根治性切除的 HCC 患者的新型预后指标。BIRC3 通过上调 MAP3K7 促进 HCC 上皮-间充质转化（EMT）、细胞迁移和转移，从而诱导 ERK1/2 磷酸化。BIRC3 的特异性抑制剂 AT-406 可抑制 HCC 细胞增殖并减少肺转移。
BIRC3 在体外和体内诱导肿瘤增殖和转移。BIRC3 可能成为肝癌的一种新的治疗靶点。
