title: miR-34a inhibits pancreatic cancer progression through Snail1-mediated epithelial-mesenchymal transition and the Notch signaling pathway.
abstract: Epithelial-mesenchymal transition (EMT) and Notch signaling are important for the growth and invasion of pancreatic cancer, which is a leading cause of cancer-related deaths worldwide. miR-34a has been shown to play pivotal roles in the progression of several types of cancer. However, little is known about the regulatory mechanisms of miR-34a in pancreatic cancer processes. The aim of this study was to determine whether miR-34a has negative effects on pancreatic cancer and whether these effects are related to EMT and Notch signaling. In vitro, we demonstrated that miR-34a inhibited, while miR-34a inhibitors enhanced, migration and invasion of pancreatic cancer cell lines (PANC-1 and SW-1990).These effects were reversed by Snail1 overexpression or Snail1 shRNA. Furthermore, the anti-apoptotic effects of the miR-34a inhibitors in pancreatic cancer cells were abrogated by Notch1 shRNA. Luciferase reporter assays revealed that the Snail1 and Notch1 genes were direct targets of miR-34a. In vivo, we also demonstrated that miR-34a inhibited pancreatic cancer growth by decreasing Snail1 and Notch1 expression. Therefore, our results indicate that miR-34a inhibits pancreatic cancer progression by post-transcriptionally regulating Snail1 and Notch1 expression.
authors.affiliation: Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Ying-Sheng
authors.initials: YS
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism*
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors