Article Abstract

IQGAP1 expression in hepatocellular carcinoma predicts poor prognosis by inducing epithelial-mesenchymal transition

Authors: Chuan Li, Tian-Fu Wen, Xiao-Yun Zhang, Xiang Chen, Jun-Yi Shen

Abstract

Background: The prognostic value of expression of the IQ motif containing GTPase activating protein 1 (IQGAP1) in hepatocellular carcinoma (HCC) following liver resection and its potential mechanism were unclear. In this study, we attempted to clarify them.
Methods: The expression of IQGAP1 in HCC and adjacent samples was assessed by immunohistochemistry staining, and its correlations with postoperative recurrence and mortality were also analyzed. Epithelial and mesenchymal markers and the invasive and migration ability of HCC cells were examined in HCC cell lines by overexpression or silencing expression of IQGAP1 using IQGAP1 plasmids or SiRNA.
Results: IQGAP1 expression was significantly increased in HCC tissues in comparison with adjacent tissues (57.78% versus 8.15%; P<0.001). Multivariate analysis suggested positive IQGAP1 expression was associated with a high incidence of postoperative recurrence and mortality. When overexpression of IQGAP1 in HCC cell lines was achieved by transfection with pFlag-IQGAP1 plasmids, the epithelial markers, E-cadherin and Claudin 1 were down regulated, whereas the mesenchymal markers N-cadherin, vimentin and MMP2 were up regulated. On the contrary, following silencing of IQGAP1 in HCC cell lines by IQGAP1-specific siRNA, high expressions of E-cadherin and Claudin 1 and low expressions of N-cadherin, vimentin and MMP2 were observed. Overexpression of IQGAP1 could also increase the invasive and migration ability of HCC cells, whereas, silencing of IQGAP1 in HCC cell lines could reduce the invasive and migration ability.
Conclusions: The positive expression of IQGAP1 in HCC was related to poor prognosis following liver resection, which may occur through induction of the epithelial-mesenchymal transition (EMT).

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