New insight into BIRC3: A novel prognostic indicator and a potential therapeutic target for liver cancer
New insight into BIRC3: A novel prognostic indicator and a potential therapeutic target for liver cancer
复制标题
对 BIRC3 的新见解：一种新的预后指标和肝癌的潜在治疗靶点
DOI：
10.1002/jcb.27890
复制
发表时间：
2019-04-01
影响因子：
4
通讯作者：
Zhou, Jian
中科院分区：
文献类型：
--
作者：
Fu, Pei-Yao;Hu, Bo;Zhou, Jian
背景 由于高复发率和无效的治疗选择，肝细胞癌（HCC）的预后仍然很差，这突出表明需要更好地了解 HCC 复发和转移的机制。方法首先收集了2009年至2010年来自癌症基因组图谱（TCGA）数据库的442例HCC患者以及中山医院251例HCC患者的信使RNA（mRNA）表达数据，分析杆状病毒IAP重复序列3（BIRC3）的组织微阵列（TMA）表达模式。然后，我们利用 BIRC3 功能获得（过度表达）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 肿瘤进展的永恒机制。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。结果 BIRC3 可以作为接受根治性切除的 HCC 患者的新预后指标。 BIRC3 通过上调 MAP3K7 促进 HCC 上皮间质转化 (EMT)、细胞迁移和转移，从而诱导 ERK1/2 磷酸化。特异性BIRC3抑制剂AT-406可以抑制HCC细胞增殖并减少肺转移。结论 BIRC3在体外和体内诱导肿瘤增殖和转移。 BIRC3可能作为肝癌的新治疗靶点。
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.