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The effect of CXCL9 on the invasion ability of hepatocellular carcinoma through up-regulation of PREX2

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Abstract

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.

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Acknowledgments

This work was supported by research grants from the National Natural Science Foundation of China (Nos. 81270507; 81100264; 81100498).

Conflict of interest

All the authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Xiaoqin Lan, Fang Xiao, Qiang Ding, Jiqiao Liu, Jingmei Liu & De-An Tian

  2. Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Xiaoqin Lan

  3. Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Junhua Li & Jiong Zhang

Authors
  1. Xiaoqin Lan
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  2. Fang Xiao
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  3. Qiang Ding
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  4. Jiqiao Liu
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  5. Jingmei Liu
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  6. Junhua Li
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  7. Jiong Zhang
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  8. De-An Tian
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Correspondence to De-An Tian.

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Xiaoqin Lan and Fang Xiao have contributed equally to this work.

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Lan, X., Xiao, F., Ding, Q. et al. The effect of CXCL9 on the invasion ability of hepatocellular carcinoma through up-regulation of PREX2. J Mol Hist 45, 689–696 (2014). https://doi.org/10.1007/s10735-014-9593-0

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  • DOI: https://doi.org/10.1007/s10735-014-9593-0

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