Shen Zhenghai, Wang Xing, Yu Xiaotian, Zhang Yun, Qin Lei
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of General Surgery, Yixing People's Hospital, Yixing, Wuxi 214200, China.
Oncotarget. 2017 Aug 7;8(42):72197-72204. doi: 10.18632/oncotarget.20060. eCollection 2017 Sep 22.
Matrix metalloproteinase (MMPs) participates in multiple biological behaviors and plays an important role in regulating tumor invasion. However, the functions of MMP16 in hepatocellular carcinoma (HCC) remains unknown. The prognostic value of MMP16 was studied in TCGA database and validation cohort. MMP16-silencing HCC cells (HepG2 and HCCLM3) were used for evaluating cell proliferation and invasion by CCK-8 and Transwell assays. Our results showed that the MMP16 was a predictor for overall survival in patients with HCC (HR: 1.169, 95% CI: 1.034-1.321, = 0.013) in TCGA database. In validation cohort, MMP16 expression was an independent predictor for survival in both univariate and multivariate analysis ( < 0.05). Furthermore, knockdown MMP16 weakened the cell invasive potential by inhibiting epithelial-mesenchymal transition (EMT) process. Therefore, our findings showed that MMP16 was a prognostic factor in HCC, ectopic MMP16 expression promoted invasion of HCC cells by inducing EMT process, suggesting a tumor oncogenic function in HCC and provides the potential therapeutic target for the treatment of HCC.
基质金属蛋白酶（MMPs）参与多种生物学行为，在调节肿瘤侵袭中起重要作用。然而，MMP16在肝细胞癌（HCC）中的功能仍不清楚。在TCGA数据库和验证队列中研究了MMP16的预后价值。使用MMP16沉默的肝癌细胞（HepG2和HCCLM3）通过CCK-8和Transwell试验评估细胞增殖和侵袭。我们的结果表明，在TCGA数据库中，MMP16是HCC患者总生存期的一个预测指标（HR：1.169，95%CI：1.034-1.321，P = 0.013）。在验证队列中，MMP16表达在单变量和多变量分析中都是生存的独立预测指标（P < 0.05）。此外，敲低MMP16通过抑制上皮-间质转化（EMT）过程削弱细胞侵袭潜能。因此，我们的研究结果表明，MMP16是HCC的一个预后因素，异位MMP16表达通过诱导EMT过程促进肝癌细胞侵袭，提示其在HCC中的肿瘤致癌功能，并为HCC的治疗提供了潜在的治疗靶点。
