The effect of CXCL9 on the invasion ability of hepatocellular carcinoma through up-regulation of PREX2
The effect of CXCL9 on the invasion ability of hepatocellular carcinoma through up-regulation of PREX2
复制标题
CXCL9通过上调PREX2对肝细胞癌侵袭能力的影响
DOI：
10.1007/s10735-014-9593-0
复制
发表时间：
2014-12-01
影响因子：
3.2
通讯作者：
Tian, De-An
中科院分区：
文献类型：
--
作者：
Lan, Xiaoqin;Xiao, Fang;Tian, De-An
研究表明，CXCL9的高表达参与了乙肝病毒感染后炎症细胞的浸润和肝损伤。然而，CXCL9是否以及通过什么潜在机制在乙肝病毒感染相关性肝细胞癌的侵袭能力中发挥作用仍不清楚。本研究以人肝细胞癌及癌旁组织和三种肝癌细胞系为研究对象，探讨CXCL9在肝癌侵袭转移调控中的作用。Transwell法检测肝癌细胞的侵袭能力，与重组人CXCL9(RhCXCL9)共培养后，肝癌细胞的侵袭能力增强。在CXCL9激活G蛋白偶联受体(GPCR)后，作为RAC GTP酶信号转导通路的一种，肝癌细胞株与rhCXCL9共同培养后，PREX2的mRNA表达增加。此外，肝细胞癌组织中PREX2的表达水平显著高于癌旁组织。此外，45对肝细胞癌组织中PREX2的表达水平与分化程度低、门静脉侵犯、转移及HBSAg定性结果呈正相关。同样，在Transwell实验中，三种肝癌细胞系中PREX2的mRNA水平均高于正常肝细胞系，而小干扰RNA(PREX2-siRNA)抑制PREX2的表达则降低了肝癌细胞的侵袭能力。总之，我们的结果提示CXCL9可能通过上调其潜在的效应因子PREX2参与了肝癌的侵袭能力。
Elevated expression of CXCL9 has been shown to involve in the infiltration of inflammatory cells and liver damage after Hepatitis B virus (HBV) infection. However, whether and by what underlying mechanism does CXCL9 play a role in HBV infection associated hepatocellular carcinoma (HCC) invasion ability remain unclear. In this study, human HCC as well as adjacent noncancerous tissues, together with three kinds of liver cancer cell lines were investigated to clarify the possible involvement of CXCL9 in the regulation of HCC invasion and metastasis. Invasion ability of liver cancer cells were evaluated by transwell assays and it is enhanced after co-cultured with recombined human CXCL9 (rhCXCL9). As a trigger of Rac GTPase signaling after G protein-coupled receptors (GPCR) activated by CXCL9, Phosphatidylinositol-3, 4, 5-trisphosphate RAC Exchanger 2 (PREX2) mRNA expression of the liver cancer cell lines was elevated after co-cultured with rhCXCL9. Moreover, the mRNA level of PREX2 in HCC tissues was significantly higher than those in adjacent noncancerous tissues. Besides, the mRNA levels of PREX2 were positively correlated with the poor differentiation, portal vein invasion, metastasis and qualitative HbsAg results in 45 pairs of HCC specimens. Similarly, PREX2 mRNA was higher in three liver cancer cell lines when compared with the normal liver cell line whereas knocked down of PREX2 by small interference RNA (PREX2-siRNA) reduced the invasion ability of liver cancer cells in transwell assays. Overall, our results suggested CXCL9 was involved in the invasion ability of HCC possibly through up-regulation of its potential effector PREX2.