Yang Ying, Liu Qiang, Zhang Hua, Zhao Huarong, Mao Ruin, Li Zhipeng, Ya Sha, Jia Chunli, Bao Yongxing
Department of Cancer Center, The First Affiliated Hospital of XinJiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
Department of Urology, The First Affiliated Hospital of XinJiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
Oncol Rep. 2017 Feb;37(2):1182-1188. doi: 10.3892/or.2017.5351. Epub 2017 Jan 4.
Epithelial-mesenchymal transition (EMT) is associated with invasion and metastasis of cancer cells. Golgi protein 73 (GP73) is a serum biomarker for hepatocellular carcinoma (HCC) and our previous study demonstrated that the expression of GP73 correlated with aggressive behavior and EMT molecules in HCC. However, its role in metastatic mechanism of HCC is not clear. The aim of this study was to investigate the effect of GP73 on invasion and migration, and underlying mechanism of GP73 involved in EMT of HCC. The expression of GP73 was downregulated by small interfering RNA (siRNA). The metastatic and invasive abilities were analyzed using scratch assay and Transwell assay. Changes in EMT-related molecules were evaluated by western blot and qRT‑PCR analyses, and epithelial-mesenchymal phenotype changes were also observed. Expression of GP73 was upregulated in the more metastatic HCC cell lines. Knockdown of GP73 by siRNA resulted in a significant decrease in migratory and invasive abilities in both MHCC97H and Bel-7404 cell lines. Importantly, EMT-related markers and morphological phenotypes significantly changed following by the inhibition of GP73. Silencing GP73 contributed to the reduction of invasion and metastasis via suppressing EMT in HCC. GP73 may serve as a novel molecular target against EMT in HCC metastasis therapy.
上皮-间质转化（EMT）与癌细胞的侵袭和转移相关。高尔基体蛋白73（GP73）是肝细胞癌（HCC）的一种血清生物标志物，我们之前的研究表明，GP73的表达与HCC的侵袭性行为和EMT分子相关。然而，其在HCC转移机制中的作用尚不清楚。本研究旨在探讨GP73对HCC侵袭和迁移的影响以及GP73参与HCC EMT的潜在机制。采用小干扰RNA（siRNA）下调GP73的表达。使用划痕试验和Transwell试验分析转移和侵袭能力。通过蛋白质免疫印迹法和qRT-PCR分析评估EMT相关分子的变化，并观察上皮-间质表型的变化。在转移性更强的HCC细胞系中，GP73的表达上调。通过siRNA敲低GP73导致MHCC97H和Bel-7404细胞系的迁移和侵袭能力显著降低。重要的是，抑制GP73后，EMT相关标志物和形态表型发生了显著变化。沉默GP73通过抑制HCC中的EMT促进侵袭和转移的减少。GP73可能作为HCC转移治疗中针对EMT的一种新型分子靶点。
