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Int J Mol Med. 2014 Dec;34(6):1599-605. doi: 10.3892/ijmm.2014.1940. Epub 2014 Sep 19.

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

Author information

1
Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China.
2
Department of Hepatobiliary Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.
3
Department of General Surgery, The Second Artillery General Hospital of PLA, Beijing 100088, P.R. China.

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.

PMID:
25242509
DOI:
10.3892/ijmm.2014.1940
[Indexed for MEDLINE]

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