title: Roles and mechanism of miR-199a and miR-125b in tumor angiogenesis.
abstract: MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA levels in ovarian tissues. We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and miR-125b-inhibiting angiogenesis responses and Akt/p70S6K1/HIF-1α pathway. This study provides a rationale for new therapeutic approach to suppress tumor angiogenesis using miR-199a, miR-125b, or their mimics for ovarian cancer treatment in the future.
authors: State Key Lab of Reproductive Medicine, Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors: Jun
authors: J
authors: He
authors: Yi
authors: Y
authors: Jing
authors: Wei
authors: W
authors: Li
authors: Xu
authors: X
authors: Qian
authors: Qing
authors: Q
authors: Xu
authors: Feng-Shan
authors: FS
authors: Li
authors: Ling-Zhi
authors: LZ
authors: Liu
authors: Bing-Hua
authors: BH
authors: Jiang
authors: Yue
authors: Y
authors: Jiang
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D042461:Vascular Endothelial Growth Factor A; C497442:HIF1A protein, human; C531888:MIRN125 microRNA, human; C531408:mirn199 microRNA, human; C508053:ERBB2 protein, human