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

被引:81
|
作者
Zhang, Jing [1 ]
Zhao, Chen-Yan [1 ]
Zhang, Shu-Hui [2 ]
Yu, Dang-Hui [1 ]
Chen, Ying [1 ]
Liu, Qing-Hua [1 ]
Shi, Min [1 ]
Ni, Can-Rong [1 ]
Zhu, Ming-Hua [1 ]
机构
[1] Second Mil Med Univ, Changhai Hosp, Dept Pathol, Shanghai 200433, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Yueyang Hosp, Dept Pathol, Shanghai 200437, Peoples R China
基金
中国国家自然科学基金;
关键词
pancreatic ductal adenocarcinoma; microRNA; diagnosis; growth; progression; targets; CANCER; MICRORNAS; GENE; METASTASIS; DIAGNOSIS; BIOMARKER; PROGNOSIS; MARKERS; DACH1; SERUM;
D O I
10.3892/or.2013.2960
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1157 / 1164
页数:8
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