MiR-9 promotes tumorigenesis and angiogenesis and is activated by MYC and OCT4 in human glioma
MiR-9 promotes tumorigenesis and angiogenesis and is activated by MYC and OCT4 in human glioma
复制标题
MiR-9 促进肿瘤发生和血管生成，并在人胶质瘤中被 MYC 和 OCT4 激活
DOI：
10.1186/s13046-019-1078-2
复制
发表时间：
2019-02-22
影响因子：
11.3
通讯作者：
Wang, Tao
中科院分区：
文献类型：
--
作者：
Chen, Xu;Yang, Fan;Wang, Tao
研究背景脑胶质瘤是一种严重威胁人类健康和生命的恶性肿瘤，预后不良，生存率低。MicroRNA-9（miR-9）参与多种肿瘤的调控，但其在人脑胶质瘤中的异常表达和功能改变的机制仍存在争议。应用获得和丧失功能测定来鉴定miR-9在体外和体内对胶质瘤细胞和HUVEC的作用。通过生物信息学预测miR-9的潜在靶点，并通过体外实验进一步验证。结果miR-9在胶质瘤标本和胶质瘤细胞中表达上调，并能显著促进胶质瘤细胞的增殖、迁移和侵袭。此外，miR-9可以通过外泌体从胶质瘤细胞中分泌，然后被血管内皮细胞吸收，导致血管生成增加。COL 18 A1、THBS 2、PTCH 1和PHD 3被证实是miR-9的直接靶点，可以阐明miR-9诱导的胶质瘤细胞恶性表型。MYC和OCT 4能够结合到miR-9的启动子区域以触发其transcription.ConclusionsOur结果强调miR-9在胶质瘤发病机制中是关键的，并且可以作为胶质瘤的潜在治疗靶点。
BackgroundGlioma, characterized by its undesirable prognosis and poor survival rate, is a serious threat to human health and lives. MicroRNA-9 (miR-9) is implicated in the regulation of multiple tumors, while the mechanisms underlying its aberrant expression and functional alterations in human glioma are still controversial.MethodsExpressions of miR-9 were measured in GEO database, patient specimens and glioma cell lines. Gain- and loss-of-function assays were applied to identify the effects of miR-9 on glioma cells and HUVECs in vitro and in vivo. Potential targets of miR-9 were predicted by bioinformatics and further verified via in vitro experiments. Transcriptional regulation of miR-9 by MYC and OCT4 was determined in glioma cells.ResultsMiR-9 was frequently up-regulated in glioma specimens and cells, and could significantly enhance proliferation, migration and invasion of glioma cells. In addition, miR-9 could be secreted from glioma cells via exosomes and was then absorbed by vascular endothelial cells, leading to an increase in angiogenesis. COL18A1, THBS2, PTCH1 and PHD3 were verified as the direct targets of miR-9, which could elucidate the miR-9-induced malignant phenotypes in glioma cells. MYC and OCT4 were able to bind to the promoter region of miR-9 to trigger its transcription.ConclusionsOur results highlight that miR-9 is pivotal for glioma pathogenesis and can be treated as a potential therapeutic target for glioma.