title: Upregulation of miR-194 contributes to tumor growth and progression in pancreatic ductal adenocarcinoma.
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.
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Chen-Yan
authors.initials: CY
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Dang-Hui
authors.initials: DH
authors.lastname: Yu
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Liu
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Can-Rong
authors.initials: CR
authors.lastname: Ni
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology; D012372:ROC Curve; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C554846:MIRN194 microRNA, human; D035683:MicroRNAs