title: Over-expression of microRNA-940 promotes cell proliferation by targeting GSK3β and sFRP1 in human pancreatic carcinoma.
abstract: Increasing study reports that Wnt/β-catenin signaling pathway plays an essential role in numerous cancers growth, progression and metastasis. Aberrant miR-940 expression has been studied in gastric and breast cancer. However, the molecular mechanism of miR-940 enhancing proliferation and metastatic ability in human pancreatic carcinoma is far from to know. Real-time PCR was used to quantify miR-940 expression. Luciferase reporter assays here were performed to verify the activity of Wnt/β-catenin signaling pathway and targeting gene relationships, and immunofluorescence assay was applied to observe β-catenin expressed intensity. Bioinformatics analysis together with in vivo and vitro functional analysis indicated the potential targeting genes of miR-940. Specimens from 15 pairs of patients with human pancreatic carcinoma were involoved to confirm the relationship between miR-940 expression and the GSK3β/sFRP1 through real-time PCR and western blot assays. Bioinformatics combined with cell luciferase function researches determined the possible regulation of miR-940 on the 3'-UTR of the GSK3β and sFRP1 genes, resulting in the Wnt/β-catenin signaling activation. Further, miR-940 knockdown significantly recovered GSK3β and sFRP1 expression and relieved Wnt/β-catenin-mediated cell invasion, migration, metastasis and proliferation. The ectopic up-regulation of miR-940 significantly suppressed GSK3β/sFRP1 expression and promoted pancreatic carcinoma proliferation and invasion. Our study suggested mechanistic relationship between miR-940 and Wnt/β-catenin in the development and progression of pancreatic carcinoma through regulation of GSK3β and sFRP1.
authors.affiliation: Department of Gastrointestinal Surgery, the first affiliated hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, Henan 450052, PR China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, the first affiliated hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, Henan 450052, PR China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, the first affiliated hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, Henan 450052, PR China.
authors.forename: Yu-Qiong
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, the first affiliated hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, Henan 450052, PR China.
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Surgery, the first affiliated hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, Henan 450052, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, the first affiliated hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, Henan 450052, PR China.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Surgery, the first affiliated hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Zhengzhou, Henan 450052, PR China.
authors.forename: Xie-Fu
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: College of Public Health, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China. Electronic address: yehua450052@139.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Ye
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000099274:Frizzled-Related Proteins
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D011506:Proteins; D000099274:Frizzled-Related Proteins; C000594732:MIRN940 microRNA, human
keywords: GSK3β; Pancreatic carcinoma; Proliferation; miR-940; sFRP1