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miR-141 通过调控 EphA2 的表达抑制脑胶质瘤血管拟态。

miR‑141 inhibits glioma vasculogenic mimicry by controlling EphA2 expression.

机构信息

Department of Neurosurgery, People's Hospital of Shiyan, Shenzhen, Guangdong 518108, P.R. China.

Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Guangzhou, Guangdong 510280, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):1395-1404. doi: 10.3892/mmr.2018.9108. Epub 2018 May 31.

Abstract

Human glioma is a pernicious tumor from the central nervous system; it has been reported that microRNAs (miRs) may have carcinogenic or tumor suppressor effects on human glioma. The aim of the present study was to assess miR‑141 expression and functional role in human primary glioma, as well as in tumor‑derived cell lines. The expression of miR‑141 in primary human glioma tissues and cell lines was assessed by employing reverse transcription‑quantitative polymerase chain reaction. Next, its role in cellular growth, migration, invasion and vasculogenic mimicry (VM) regulation was determined using various in vitro and in vivo assays, and on the identification its target gene(s) using luciferase assays. The results demonstrated that miR‑141 expression was downregulated, and Ephrin type‑A receptor 2 (EphA2) was upregulated in the primary human gliomas and human glioma‑derived cell lines tested. In addition, a negative correlation existed between miR‑141 and EphA2 expression levels in glioma grades II, III and IV. Furthermore, exogenous miR‑141 expression resulted in decreased proliferation, migration and invasion, as well as in apoptosis and cell cycle arrest in vitro. It was also revealed that exogenous miR‑141 expression resulted in in vivo inhibition of tumor growth and inhibition of the development of VM. Finally, the present study successfully confirmed that EphA2 was a direct target of miR‑141 in glioma‑derived cells using luciferase assays. Based on these results, it was concluded that miR‑141 may regulate cell proliferation, migration, invasion and VM formation by controlling EphA2 expression; also, its target EphA2 may be a novel diagnostic/prognostic biomarker and a potential anti‑VM therapeutic target.

摘要

人类脑胶质瘤是一种源自中枢神经系统的恶性肿瘤;据报道,微小 RNA(miRs)可能对人类脑胶质瘤具有致癌或肿瘤抑制作用。本研究旨在评估 miR-141 在人原发性脑胶质瘤以及肿瘤衍生细胞系中的表达和功能作用。采用逆转录-定量聚合酶链反应评估 miR-141 在原发性人脑胶质瘤组织和细胞系中的表达。接下来,通过各种体外和体内测定,以及通过荧光素酶测定鉴定其靶基因(s),确定其在细胞生长、迁移、侵袭和血管生成模拟(VM)调节中的作用。结果表明,在测试的原发性人胶质瘤和人胶质瘤衍生细胞系中,miR-141 表达下调,Eph 型-A 受体 2(EphA2)上调。此外,miR-141 和 EphA2 表达水平在胶质瘤 II、III 和 IV 级之间存在负相关。此外,外源性 miR-141 表达导致体外增殖、迁移和侵袭减少,以及凋亡和细胞周期停滞。还发现外源性 miR-141 表达导致体内肿瘤生长抑制和 VM 发育抑制。最后,本研究成功地通过荧光素酶测定证实 EphA2 是胶质瘤衍生细胞中 miR-141 的直接靶标。基于这些结果,得出结论,miR-141 可能通过控制 EphA2 表达来调节细胞增殖、迁移、侵袭和 VM 形成;此外,其靶 EphA2 可能是一种新的诊断/预后生物标志物和潜在的抗 VM 治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8228/6072184/a23e4ba820b3/MMR-18-02-1395-g00.jpg

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