Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A.
Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A.
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miR-126表达减少通过调节VEGF-A促进胃癌血管生成
DOI：
10.18632/oncotarget.2662
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发表时间：
2014-12-15
期刊：
影响因子：
--
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Chen H;Li L;Wang S;Lei Y;Ge Q;Lv N;Zhou X;Chen C
miR-126是一种内皮特异性microRNA，对控制血管完整性和血管生成至关重要。其在胃癌血管生成中的作用尚不清楚。本研究旨在确定miR-126在GC血管生成中的作用。胃癌组织中miR-126表达下调与微血管密度（MVD）和血管内皮生长因子A（VEGF-A）表达增加呈负相关。生物信息学分析和荧光素酶报告基因分析表明，miR-126直接靶向VEGF-A mRNA的3′-非翻译区（3′-UTR）。此外，慢病毒-miR-126（Lenti-miR-126）转染恢复miR-126表达后，胃癌细胞株SGC-7901、MKN-28和MKN-45中VEGF-A的表达及其下游基因Akt、mTOR和Erk 1/2的活性明显降低。相反，慢病毒-抗miR-126（Lenti-anti-miR-126）转染下调miR-126表达后，VEGF-A及其下游信号通路的表达明显上调。体内异种移植小鼠模型实验阐明了VEGF-A和MVD的下调以及通过上调miR-126抑制肿瘤生长。总之，我们的研究结果提示miR-126可以通过VEGF-A信号通路抑制胃癌的肿瘤生长和肿瘤血管生成，是胃癌治疗的一个新的潜在靶点。
miR-126 is an endothelial-specific microRNA essential for governing vascular integrity and angiogenesis. Its role in tumor angiogenesis of gastric cancer (GC) is unclear. This study aimed at determining the role of miR-126 in GC angiogenesis. Down-regulation of miR-126 was found to inversely correlate with an increased microvessel density (MVD) and vascular endothelial growth factor A (VEGF-A) expression in gastric cancer tissues. Bioinformatics analysis and luciferase reporter assay revealed that miR-126 directly targeted the 3′-untranslated region (3′-UTR) of VEGF-A mRNA. In addition, the restoration of miR-126 expression by lentivirus-miR-126 (Lenti-miR-126) transfection obviously reduced the expression of VEGF-A and the activition of its downstream genes, Akt, mTOR and Erk1/2 in gastric cancer cell lines SGC-7901, MKN-28 and MKN-45. In contrast, the down-regulation of miR-126 expression by lentivirus-anti-miR-126 (Lenti-anti-miR-126) transfection obviously up-regulated the expression of VEGF-A and its downstream signaling pathways. In vivo xenograft mice model experiments clarified the down-regulation of VEGF-A and MVD as well as inhibition of tumor growth by up-regulation of miR-126. Overall, the results from our study suggested that miR-126 could suppress tumor growth and tumor angiogenesis of GC through VEGF-A signaling, and it is a novel potential therapeutic target for GC.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
3.7
作者：
Feng X;Wang H;Ye S;Guan J;Tan W;Cheng S;Wei G;Wu W;Wu F;Zhou Y
通讯作者：
Zhou Y
影响因子：
5.2
作者：
Liu, Li Ying;Wang, Wei;Xu, Ji Ru
通讯作者：
Xu, Ji Ru
影响因子：
82.9
作者：
Bonci, Desiree;Coppola, Valeria;De Maria, Ruggero
通讯作者：
De Maria, Ruggero
DOI：
10.1007/978-1-60761-863-8_13
发表时间：
2011-01-01
期刊：
MICRORNA AND CANCER: METHODS AND PROTOCOLS
影响因子：
--
作者：
Li, Zejuan;Chen, Jianjun
通讯作者：
Chen, Jianjun