Upregulation of miR-194 contributes to tumor growth and progression in pancreatic ductal adenocarcinoma

Zhang,Jing; Zhao,Chen-Yan; Zhang,Shu-Hui; Yu,Dang-Hui; Chen,Ying; Liu,Qing-Hua; Shi,Min; Ni,Can-Rong; Zhu,Ming-Hua

doi:10.3892/or.2013.2960

Upregulation of miR-194 contributes to tumor growth and progression in pancreatic ductal adenocarcinoma

Authors:
- Jing Zhang
- Chen-Yan Zhao
- Shu-Hui Zhang
- Dang-Hui Yu
- Ying Chen
- Qing-Hua Liu
- Min Shi
- Can-Rong Ni
- Ming-Hua Zhu
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Affiliations: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China, Department of Pathology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China
Published online on: December 31, 2013 https://doi.org/10.3892/or.2013.2960
Pages: 1157-1164

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of human cancer worldwide. In the present study, we investigated the diagnostic and biological significance of microRNA-194 (miR-194) in PDAC. miRNA expression profiling of human PDACs and adjacent normal pancreatic tissues identified a total of 16 genes including miR-194 with >1.15-fold expression changes (8 overexpressed and 8 underexpressed). Quantitative real-time polymerase chain reaction (PCR) revealed elevation of serum miR-194 levels were significantly greater in PDAC patients than in duodenal adenocarcinoma patients and healthy controls. Receiver operating characteristic analysis demonstrated that serum miR-194 had a sensitivity of 54.3% and a specificity of 57.5% for discriminating PDAC patients from healthy controls. Combined analysis of the 3 groups yielded a sensitivity of 84.0 and a specificity of 75.0% for the combined detection of miR-192 and miR-194 in the diagnosis of PDAC. Ectopic expression of miR-194 in PANC-1 pancreatic cancer cells enhanced cell proliferation, migration and colony formation, which was coupled with decreased expression of the tumor suppressor DACH1. miR-194 overexpression increased tumor growth and local invasion and suppressed the expression of DACH1 in an orthotopic pancreatic cancer mouse model. In conclusion, upregulation of miR-194 contributes to tumor growth and progression in PDAC, possibly through suppression of DACH1. However, serum miR-194 has a low capacity for detection of PDAC. Combined detection of serum miR-192 and miR-194 levels may serve as a sensitive diagnostic biomarker for PDAC.

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