title: MiR-145 functions as a tumor suppressor targeting NUAK1 in human intrahepatic cholangiocarcinoma.
abstract: 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.
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
authors.forename: Xinkui
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
authors.forename: Daoyi
authors.initials: D
authors.lastname: Sun
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chai
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
authors.forename: Wengang
authors.initials: W
authors.lastname: Shan
authors.affiliation: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Pu
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China. Electronic address: docchengfeng@njmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
mesh_terms: D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004338:Drug Combinations; D007797:Laminin; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D011509:Proteoglycans; D012097:Repressor Proteins; C059485:matrigel; D003094:Collagen; D008156:Luciferases; D011494:Protein Kinases; C470845:NUAK1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: AKT; Intrahepatic cholangiocarcinoma; Matrix metalloproteinase protein; MiR-145; NUAK1