MiR-145 Functions As A Tumor Suppressor Targeting NUAK1 In Human Intrahepatic Cholangiocarcinoma

The dysregulation of micro(mi)RNAs is associated with cancer development.The miRNA miR-145 is downregulated in intrahepatic cholangiocarcinoma(ICC).However,its precise role in tumor progression have not yet been elucidated.Novel(nua)kinase family(NUAK)1 functions as an oncogene in various cancers and is a putative target of miR-145 regulation.In this study,we investigated the regulation of NUAKl by miR-145 in ICC.We found that miR-145 level was significantly decreased in ICC tissue and cell lines,which corresponded with an increase in NUAKl expression.NUAK1 was found to be a direct target of miR-145 regulation.The overexpression of miR-145 in ICC cell lines inhibited proliferation,growth,and invasion by suppressing NUAKl expression,which was associated with a decrease in Akt signaling and matrix metalloproteinase protein expression.Similar results were observed by inhibiting NUAK1 expression.These results demonstrate that miR-145 can prevent ICC progression by targeting NUAKl and its downstream effectors,and can therefore be useful for clinical diagnosis and targeted therapy of ICC.