关键词: miR-145, 新式激酶家族1, 肝内胆管细胞癌, 蛋白激酶B

Abstract: Objective To investigate the specific mechanism of miR-145 regulating cell proliferation of human intrahepatic cholangiocarcinoma (ICC). Methods 38 pairs of ICC tissues and adjacent tissues were collected. At the same time, to investigate miR-145 function in ICC cells, HuCCT-1 and RBE ICC cell lines were transfected with miR-145 mimics and siRNA-mediated knockdown of NUAK1. The expression of miR-145 and NUAK1 was detected by RT-qPCR. And cell proliferation was observed by cell proliferation and cycle analysis. The target genes of miR-145 were confirmed by the luciferase report. The protein level of AKT pathway was studied by Western blot. Results The expressions of miR-145 in cancer tissues were significantly lower than that in adjacent tissues (p<0.05). While NUAK1 expressions in cancer tissues were significantly higher than that in adjacent tissues (p<0.05), and there was a certain correlation between them. The cell counts of the miR-145 overexpression group and the NUAK1 interference group were less compared with the negative control group (p<0.05). The number of cells in the G1 phase were increased markedly (p<0.05). Furthermore, the wild type fluorescence signal was suppressed significantly (p<0.05). The expression of pAKT and pFOXO1 was significantly decreased, while tAKT and tFOXO1 showed no significant change (p<0.05). Conclusion miR-145 may prevent ICC proliferation by targeting NUAK1 and its downstream effectors, and can therefore be useful for clinical diagnosis and targeted therapy of ICC.

Key words: miR-145, Novel (nua) kinase family (NUAK)1, intrahepatic cholangiocarcinoma, protein kinase B