title: miR‑96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer.
abstract: microRNA-96 (miR-96) is known to be downregulated in pancreatic cancer. The overexpression of miR-96 in MIA PaCa-2 pancreatic cancer cells has been shown to inhibit cell proliferation, migration and invasion; however, the mechanisms involved have not yet been fully elucidated. Novel (nua) kinase family 1 (NUAK1) functions as an oncogene in non‑small cell lung cancer (NSCLC), melanoma, glioma, breast cancer, hepatocellular carcinoma and pancreatic cancer. In this study, firstly, we demonstrate that NUAK1 expression is specifically upregulated in pancreatic cancer and that it promotes the proliferation, migration and invasion of MIA PaCa-2 pancreatic cancer cells. Secondly, we performed an analysis of potential microRNA (miRNA) target sites using three commonly used prediction algorithms: miRanda, TargetScan and PicTar. All three algorithms predicted that miR-96 targets the 3' untranslated region (3' UTR) of NUAK1. Further experiments confirmed this prediction, namely that miR-96 suppresses the expression of NUAK1 by targeting its 3' UTR. Finally, we demonstrate that the introduction of NUAK1 cDNA lacking predicted sites of the 3' UTR abrogates miR-96 cellular function.
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of General Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China.
authors.forename: Da-Lin
authors.initials: DL
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D011494:Protein Kinases; C470845:NUAK1 protein, human