Long non-coding RNA H19 regulates glioma angiogenesis and the biological behavior of glioma-associated endothelial cells by inhibiting microRNA-29a
Long non-coding RNA H19 regulates glioma angiogenesis and the biological behavior of glioma-associated endothelial cells by inhibiting microRNA-29a
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DOI：
10.1016/j.canlet.2016.08.009
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发表时间：
2016-10-28
期刊：
影响因子：
9.7
通讯作者：
Xue, Yixue
中科院分区：
文献类型：
--
作者：
Jia, Peng;Cai, Heng;Xue, Yixue
长链非编码RNA（lncRNA）在胶质瘤的发生发展中起着重要作用。研究表明IncRNA H19调控肿瘤的发生、血管生成和转移。本研究旨在探讨其在胶质瘤诱导的内皮细胞增殖、迁移和管腔形成中的作用及其可能的分子机制。H19在胶质瘤组织的微血管和胶质瘤相关内皮细胞（GEC）中表达上调。H19基因的敲除可抑制胶质瘤诱导的内皮细胞增殖、迁移和管腔形成，同时上调miR-29 a的表达。生物信息学分析和荧光素酶报告基因分析证实H19通过与miR-29 a直接结合而介导上述效应。此外，miR-29 a靶向血管收缩素2（VASH 2）的3 '-UTR区域并降低其表达。VASH 2已被鉴定为血管生成因子。H19的敲除还通过上调miR-29 a来降低VASH 2的表达。结论：H19基因敲除通过抑制microRNA-29 a抑制胶质瘤血管生成，可能通过调节胶质瘤血管内皮细胞的生物学行为调控胶质瘤的发生。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Long non-coding RNAs (IncRNAs) play crucial roles in the development and progression of glioma. Previous studies indicated that IncRNA H19 regulated tumor carcinogenesis, angiogenesis and metastasis. This study aimed to investigate its functional role in glioma-induced endothelial cell proliferation, migration and tube formation as well as its possible molecular mechanisms. H19 was up-regulated in microvessels from glioma tissues and glioma-associated endothelial cells (GEC) cultured in glioma conditioned medium. Knockdown of H19 suppressed glioma-induced endothelial cell proliferation, migration and tube formation in vitro and meanwhile up-regulated the expression of miR-29a. Bioinformatics analysis and luciferase reporter assay defined that H19 mediated the above effects via directly binding to miR-29a. In addition, miR-29a targeted 3'-UTR region of vasohibin 2 (VASH2) and decreased its expression. VASH2 has been identified as an angiogenic factor. Knockdown of H19 also decreased the VASH2 expression by up-regulating miR-29a. In conclusion, the results indicated that knockdown of H19 suppressed glioma induced angiogenesis by inhibiting microRNA-29a, which may modulate the onset of glioma by regulating biological behaviors of glioma vascular endothelial cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.