Role of linc00174/miR-138-5p (miR-150-5p)/FOSL2 Feedback Loop on Regulating the Blood-Tumor Barrier Permeability
Role of linc00174/miR-138-5p (miR-150-5p)/FOSL2 Feedback Loop on Regulating the Blood-Tumor Barrier Permeability
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DOI：
10.1016/j.omtn.2019.10.031
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发表时间：
2019-12-06
影响因子：
8.8
通讯作者：
Xue, Yixue
中科院分区：
文献类型：
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作者：
Guo, Jizhe;Shen, Shuyuan;Xue, Yixue
血肿瘤屏障（BTB）限制了化疗药物向脑肿瘤组织的转运，影响了胶质瘤的治疗。长链非编码rna在肿瘤的各种生物学过程中发挥着重要作用；然而，这些在BTB通透性中的作用尚不清楚。在这项研究中，我们发现长基因间非蛋白编码RNA 174 （linc00174）在胶质瘤组织的胶质瘤内皮细胞（GECs）中上调。此外，linc00174在体外BTB模型的gec中也上调。敲低linc00174增加BTB通透性，降低紧密连接相关蛋白ZO-1、occludin和claudin-5的表达。生物信息学数据和荧光素酶报告基因检测结果均表明，linc00174通过结合miR-138-5p和miR-150-5p调节BTB的通透性。此外，敲低linc00174通过上调miR-138-5p和miR-150-5p抑制FOSL2的表达。FOSL2与启动子区域相互作用，上调gec中ZO-1、occludin、claudin-5和linc00174的启动子活性。总之，本研究表明，linc00174/miR-138-5p (miR-150-5p)/FOSL2反馈回路在调节BTB通透性中发挥了重要作用。
The blood-tumor barrier (BTB) limits the transport of chemotherapeutic drugs to brain tumor tissues and impacts the treatment of glioma. Long non-coding RNAs play critical roles in various biological processes of tumors; however, the function of these in BTB permeability is still unclear. In this study, we have identified that long intergenic non-protein coding RNA 174 (linc00174) was upregulated in glioma endothelial cells (GECs) from glioma tissues. Additionally, linc00174 was also upregulated in GECs from the BTB model in vitro. Knock down of linc00174 increased BTB permeability and reduced the expression of the tight junction-related proteins ZO-1, occludin, and claudin-5. Both bioinformatics data and results of luciferase reporter assays demonstrated that linc00174 regulated BTB permeability by binding to miR-138-5p and miR-150-5p. Furthermore, knock down of linc00174 inhibited FOSL2 expression via upregulating miR-138-5p and miR-150-5p. FOSL2 interacted with the promoter regions and upregulated the promoter activity of ZO-1, occludin, claudin-5, and linc00174 in GECs. In conclusion, the present study demonstrated that the linc00174/miR-138-5p (miR-150-5p)/FOSL2 feedback loop played an essential role in regulating BTB permeability.