Background and Aims: The tumor suppressor gene HIV-1 Tat interactive protein 2 (TIP30) is down-regulated or absent in many human tumors, and is related to the poor prognosis of patients. However, there is no report about TIP30 in intrahepatic cholangiocarcinoma (ICC). Therefore, this study was performed to investigate the expression of TIP30 in ICC and its clinical significance. 
Methods: The TIP30 expressions in 51 paired specimens of ICC tissue and tumor adjacent tissue were detected by immunohistochemical staining. The relations of TIP30 expression in ICC tissues with the clinicopathologic features as well as the overall survival rate and cumulative recurrence rate of ICC patients were analyzed. The change in colony-forming ability in ICC cells (ICC-9810, SSP-25 and HuH-28) after transfection with TIP30-shRNA were determined by soft agar colony formation assay. The potential miRNAs targeting the 3’UTR of TIP30 were predicted using TargetScan and miRDB databases, and then the results were further verified by qRT-PCR.
Results: The results of immunohistochemical staining demonstrated that the expression level of TIP30 in ICC tissue was lower than that in adjacent tissue. The results of clinical data analysis indicated that the TIP30 expression was significantly associated with lymph node metastasis (P=0.008). The survival analysis showed that the 5-year overall survival rate was significantly higher (P=0.041 2), while the cumulative recurrence rate was significantly lower (P=0.037 4) in patients with high TIP30 expression than those in patients with low TIP30 expression. The number of colony-forming units in ICC cells (ICC-9810, SSP-25 and HuH-28) transfected with TIP30-shRNA were significantly increased over the negative controls (all P<0.001). The results of database prediction suggested that miR-124-3p could recognize and bind to the 3' UTR of TIP30. The results of qRT-PCR verification revealed that the relative content of miR-124-3p in ICC tissue was significantly higher than that in adjacent tissue (P<0.001); the expressions of TIP30 in ICC cells (9810, SSP-25 and HuH-28) transfected with miR-124-3p were lower than those in their negative controls (all P<0.05).
Conclusion: The TIP30 expression is down-regulated in ICC, and is closely related to the poor prognosis of ICC patients. The mechanism may be associated with the regulation mediated by miR-124-3p. The results of this study may provide information and basis for future studies on the pathogenesis and molecular target therapy of ICC.