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 has 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 NUAK1 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 NUAK1 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 NUAK1 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 NUAK1 and its downstream effectors, and can therefore be useful for clinical diagnosis and targeted therapy of ICC.
['Xiong|Xinkui|X|', 'Sun|Daoyi|D|', 'Chai|Hao|H|', 'Shan|Wengang|W|', 'Yu|Yue|Y|', 'Pu|Liyong|L|', 'Cheng|Feng|F|']
D001650:Bile Duct Neoplasms D001653:Bile Ducts, Intrahepatic D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D018281:Cholangiocarcinoma D003094:Collagen D004338:Drug Combinations D015972:Gene Expression Regulation, Neoplastic D017930:Genes, Reporter D006801:Humans D007797:Laminin D008156:Luciferases D053511:Matrix Metalloproteinase 14 D020778:Matrix Metalloproteinase 2 D020780:Matrix Metalloproteinase 9 D035683:MicroRNAs D011485:Protein Binding D011494:Protein Kinases D011509:Proteoglycans D051057:Proto-Oncogene Proteins c-akt D012097:Repressor Proteins D015398:Signal Transduction
MiR-145 NUAK1 Intrahepatic cholangiocarcinoma AKT Matrix metalloproteinase protein