title: hsa-miR-141 downregulates TM4SF1 to inhibit pancreatic cancer cell invasion and migration.
abstract: Expression of the transmembrane-4-L-six-family-1 (TM4SF1) is high in human pancreatic cancer cells, but the underlying mechanism remains unclear. In this study, we aimed to identify and characterize microRNAs that regulate TM4SF1 expression in PC cells. Western blot analysis and quantitative polymerase chain reaction were used to detect TM4SF1 and hsa-miR-141 levels in four PC cell lines. SW1990 and BxPc-3 cells were transfected with the inhibitor miR-141, the inhibitor negative control, the miR-141 mimic and the mimic negative control; and cell invasion, migration, proliferation, cell cycle progression and apoptosis were detected by Transwell, MTT and flow cytometry assays, respectively. The miR-141 levels negatively correlated with the TM4SF1 protein levels in PC cells. The TM4SF1 protein levels were lower in the 141M group but higher in the 141I group, although the TM4SF1 mRNA levels had no significant changes, compared to the negative controls. Luciferase assays demonstrated that hsa-miR-141 directly targeted the 3'-untranslated region of the TM4SF1 gene. In addition, miR-141 downregulated TM4SF1 expression to inhibit invasion and migration of PC cells but had no effects on cell proliferation, cell cycle progression or apoptosis. TM4SF1 is a direct target of miR-141. Our findings that TM4SF1 expression was inhibited by miR-141 provide new insights into the oncogenic mechanism of TM4SF1 and suggest that miR-141 represents a novel molecular target for PC therapy.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210018, P.R. China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of General Surgery, Gaochun People's Hospital, Nanjing 211300, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210018, P.R. China.
authors.forename: Qingguang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Miao
mesh_terms: D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000954:Antigens, Surface; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C074075:TM4SF1 protein, human