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微小 RNA-518b 通过靶向 PDGFRB 在胶质母细胞瘤中发挥肿瘤抑制作用。

MicroRNA‑518b functions as a tumor suppressor in glioblastoma by targeting PDGFRB.

机构信息

Department of Neurosurgery, The Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200072, P.R. China.

Department of Neurosurgery, The 411th Hospital of PLA, Shanghai 200081, P.R. China.

出版信息

Mol Med Rep. 2017 Oct;16(4):5326-5332. doi: 10.3892/mmr.2017.7298. Epub 2017 Aug 21.

Abstract

Glioblastoma (GBM) is the most common and aggressive type of primary human brain tumor in China. Dysregulated microRNA (miRNA/miR) expression has been hypothesized to serve a role in the tumorigenesis and progression of human GBM. To explore the potential mechanisms affecting GBM tumorigenesis, the function of miR‑518b in regulating GBM cell proliferation and angiogenesis was examined in vitro by CCK‑8 and tube formation assay and in vivo by xenograft assay. The present study demonstrated that the expression of miR‑518b was downregulated in GBM tissues and in GBM cell lines (U87 and U251). In addition, the expression levels of miR‑518b were highly associated with tumor size, World Health Organization grade and prognosis. Furthermore, overexpression of miR‑518b suppressed GBM cell proliferation and angiogenesis, and induced GBM cell apoptosis in vitro and in vivo. Overexpression of miR‑518b also inhibited the expression of platelet‑derived growth factor receptor β (PDGFRB), and the present study confirmed that the 3' untranslated region (3'UTR) of PDGFRB was a direct target of miR‑518b. In conclusion, to the best of our knowledge, the present study is the first to present evidence suggesting that miR‑518b may serve as a potential marker and target in GBM treatment.

摘要

胶质母细胞瘤(GBM)是中国最常见和侵袭性最强的原发性人脑肿瘤。失调的 microRNA(miRNA/miR)表达被假设在人类 GBM 的肿瘤发生和进展中起作用。为了探索影响 GBM 肿瘤发生的潜在机制,通过 CCK-8 和管形成测定以及异种移植测定,在体外和体内研究了 miR-518b 调节 GBM 细胞增殖和血管生成的功能。本研究表明,miR-518b 在 GBM 组织和 GBM 细胞系(U87 和 U251)中表达下调。此外,miR-518b 的表达水平与肿瘤大小、世界卫生组织分级和预后高度相关。此外,miR-518b 的过表达抑制了 GBM 细胞的增殖和血管生成,并在体外和体内诱导了 GBM 细胞凋亡。miR-518b 的过表达还抑制了血小板衍生生长因子受体β(PDGFRB)的表达,本研究证实 PDGFRB 的 3'非翻译区(3'UTR)是 miR-518b 的直接靶标。总之,据我们所知,本研究首次提出证据表明,miR-518b 可能作为 GBM 治疗的潜在标志物和靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96f4/5647064/98a32d58be7e/MMR-16-04-5326-g00.jpg

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