title: miR-139 and miR-200c regulate pancreatic cancer endothelial cell migration and angiogenesis.
abstract: Pancreatic cancer remains the fourth deathliest cancer worldwide with a 5-year survival rate of only 4%. The present study tested the hypothesis that dysregulated microRNA (miRNA) expression by pancreatic cancer endothelial cells (CECs) may regulate angiogenesis. Primary EC cultures were established from the pancreatic tumor and adjacent normal tissues of three pancreatic cancer patients. A miRNA microarray was used to identify miRNAs that were differentially expressed. The expression patterns of four highly expressed miRNAs in CECs were confirmed by qPCR analysis. The effects of dysregulated miRNA expression on CEC proliferation, migration and tube formation were determined after transfection with specific miRNA inhibitors. The expression of 14 miRNAs was increased by >20-fold in the the CECs of all three pancreatic patients; the increased expression of miR-200c and miR-139 in CECs was confirmed. miR-1, mir-139 and miR-200c inhibitors significantly reduced CEC migration (all P<0.05), yet not proliferation. The average tube length and total loop number were also significantly decreased upon miR-139 and miR-200c inhibition in all three CEC cultures (all P<0.05). Upregulation of miR-139 and miR-200c expression may increase CEC migration and tube formation, which suggests that these miRNAs may regulate pancreatic tumor angiogenesis.
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.
authors.forename: Baiwen
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.
authors.forename: Dafan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.
authors.forename: Lungen
authors.initials: L
authors.lastname: Lun
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Wan
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C555098:MIRN139 microRNA, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs