Chloride intracellular channel 1 participates in migration and invasion of hepatocellular carcinoma by targeting maspin

Abstract Background and Aim Our previous proteomic research found that chloride intracellular channel 1 ( CLIC 1) was upregulated in hepatocellular carcinoma ( HCC ) tissues with portal vein tumor thrombus. The present study aimed to determine the role of CLIC 1 in HCC invasion. Methods Immunohistochemistry was used to explore protein expression of CLIC 1 in 15 cirrhotic tissues and 69 pairs of HCC and paracarcinoma tissues. Small interfering RNA ( siRNA ) and plasmids were transfected into HepG2 and SMMC 7721 cells, and the in vitro function of CLIC 1 in these cells were assessed with cell counting kit‐8 assays, cell apoptosis assays, scratch assays, and transwell assays. Microarray analysis was also performed to further explore the candidate genes related to CLIC 1. Results Our results confirmed that upregulated CLIC 1 expression was significantly correlated with vascular invasion ( P = 0.034) in HCC tissues. Knockdown of CLIC 1 decreased cell viability and the invasive potency of HepG 2 cells, whereas CLIC 1 overexpression resulted in an opposite effect in SMMC 7721 cells. Microarray analysis identified 618 genes that were differentially expressed (fold change ≥ 2, P < 0.05) between HepG 2 cells transfected with CLIC 1 siRNA and the negative control. Further studies indicate that knockdown of CLIC 1 increased maspin expression and reduced vascular endothelial growth factor ( VEGF ), matrixmetalloproteinase‐2 ( MMP 2), MMP 9, MMP 11, and MMP 12 expression. In contrast, overexpression of CLIC 1 decreased maspin expression and increased VEGF , MMP 2, MMP 12, and MMP 13 expression. Conclusions CLIC 1 protein expression is significantly correlated with vascular invasion, and the present study suggests a previously unknown mechanism of CLIC 1‐mediated control of HCC invasiveness by targeting maspin.