Expression Of TIP30 In Intrahepatic Cholangiocarcinoma And Its Significance

Objective To investigate the expression of HIV-1 Tat interactive protein2(TIP30)in intrahepatic cholangiocarcinoma(ICC)and its significance.Methods Expression of TIP30 in 51 paired specimens of ICC tissues compared to adjacent normal tissues was comparatively analysed by Immunohistonchemistry.Clinical significance of TIP30 expression was revealed by correlations between TIP30 expression and clinicopathologic characteristics of ICC patients.Kaplan–Meier survival analyses showed the correlation between TIP30 expression and overall survival as well as cumulative incidence of relapse.Colony formation assays was applied to explore the impact of TIP30 upon proliferation of ICC cells.The number of potential miRNAs targeting the 3'UTR of TIP30 was predicted by two databases,Target Scan and miRDB,which is further confirmed by qRT-PCR.Results Representative IHC staining showed expression level of TIP30 was decreased in the ICC tissue compared with its tumor adjacent tissue.An analysis of 51 paired tissues further demonstrated that expression of TIP30 was significantly down-regulated in 36 pairs ICC tissues compared with their adjacent tissues(P<0.05).The TIP30 expression in ICC was markedly associated with lymphatic invasion(P=0.008).The 5-year overall survival rate in patients with high TIP30 expression was significantly higher than that in patients with low TIP30 expression(P=0.0412);while the cumulative incidence of relapse rate in patients with higher TIP30 expression was considerably lower than that in patients with low TIP30 expression(P=0.0374).Number of colonies formed from ICC cells(ICC-9810,SSP-25 and HuH-28)transfected with shTIP30 were significantly increased over negative controls,respectively(all P<0.001).miRNA target-predicting algorithms,TargetScan and miRDB,were analysed to identify potential miRNAs that bind to 3' UTR of TIP30.miR-124-3p was identified as a possible miRNA,which regulates expression of TIP30 in ICC cells(ICC-9810,SSP-25 and HuH-28).Conclusion Expression of TIP30 is down-regulated in ICC and is closely related to the poor prognosis of ICC patients.This mechanism may be mediated by miR-124-3p in ICC cancer cells.