title: MiR-146a enhances angiogenic activity of endothelial cells in hepatocellular carcinoma by promoting PDGFRA expression.
abstract: Endothelial cells (ECs) are critical for angiogenesis, and microRNAs play important roles in this process. We investigated the regulatory role of microRNAs in ECs of hepatocellular carcinoma (HCC) by examining the microRNA expression profile of human umbilical vein endothelial cells (HUVECs) in the absence or presence of human HCC cells, and identified miR-146a as the most highly upregulated microRNA. Furthermore, we revealed that miR-146a promoted the expression of platelet-derived growth factor receptor α (PDGFRA) in HUVECs, and this process was mediated by BRCA1. Overexpression of PDGFRA in the ECs of HCC tissues was associated with microvascular invasion and predicted a poorer prognosis. These results suggest that miR-146a plays a key role in regulating the angiogenic activity of ECs in HCC through miR-146a-BRCA1-PDGFRA pathway. MiR-146a and PDGFRA may emerge as potential anti-angiogenic targets on ECs for HCC therapy.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Ling-Qun
authors.initials: LQ
authors.lastname: Kong
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Xin-Rong
authors.initials: XR
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Wan
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Zhao
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Tao
authors.forename: Zong-Tao
authors.initials: ZT
authors.lastname: Chai
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zeng
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D020796:Receptor, Platelet-Derived Growth Factor alpha