miR-96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer

• Published in: International journal of molecular medicine Vol. 34; no. 6; pp. 1599 - 1605
• Main Authors: HUANG, XUAN, LV, WEI, ZHANG, JIAN-HUA, LU, DA-LIN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.12.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: 3' Untranslated Regions - genetics; Adenosine; Algorithms; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Western; Breast cancer; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Gene expression; Gene Expression Regulation, Neoplastic; Gene Silencing; Genes, Tumor Suppressor; Genetic aspects; Health aspects; Hospitals; Humans; Kinases; Medical prognosis; Metastasis; MicroRNA; microRNA-96; MicroRNAs - genetics; novel (nua) kinase family 1; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Physiological aspects; Plasmids; Protein Kinases - genetics; Protein Kinases - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Risk factors; Tumor suppressor genes; Tumorigenesis; Up-Regulation; China; United States > US
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2014.1940

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.