Department of Neurosurgery, The Affiliated Huai'an First Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7821-7828. doi: 10.3892/mmr.2017.7586. Epub 2017 Sep 21.
Glioma is the most common malignant brain tumor in adults and represents one of the most aggressive and life‑threatening types of cancer in humans. Increasing studies have revealed that microRNAs are abnormally expressed in various types of human cancer, and have oncogenic or tumor suppressive roles, which depend primarily on the type of cancer. The present study aimed to investigate the expression level and effects of microRNA‑186 (miR‑186) on glioma, and its underlying molecular mechanism. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis was performed to detect the expression of miR‑186 in glioma tissues and cell lines. Cell proliferation and invasion were assessed using MTT and cell invasion assays, respectively. Bioinformatics analysis and a luciferase reporter assay were performed to identify insulin‑like growth factor 1 receptor (IGF‑1R) as a novel target gene of miR‑186. The mRNA expression level of IGF‑1R was also measured using RT‑qPCR analysis. The association between miR‑186 and the expression of IGF‑1R was evaluated using Spearman's correlation anal-ysis. Furthermore, the regulatory effects of miR‑186 on the mRNA and protein expression of IGF‑1R were determined using RT‑qPCR and western blot analyses. Finally, the biological effects of the underexpression IGF‑1R on glioma cells were investigated. The results showed that miR‑186 was significantly downregulated in glioma tissues and cell lines. Inducing the expression of miR‑186 suppressed glioma cell proliferation and invasion. IGF‑1R was confirmed as a direct target gene of miR‑186. In addition, the mRNA expression of IGF‑1R was upregulated and inversely correlated with that of miR‑186 in glioma tissues. The effects of IGF‑1R‑knockdown on glioma cell proliferation and invasion were similar to the effects induced by the overexpression of miR‑186. These findings demonstrated that miR‑186 acted as a tumor suppressor by targeting IGF‑1R in glioma, suggesting miR‑186 may be a potential therapeutic target for the treatment of this disease.
神经胶质瘤是成人中最常见的恶性脑肿瘤，是人类最具侵袭性和致命性的癌症类型之一。越来越多的研究表明，微小 RNA 在各种人类癌症中表达异常，具有致癌或肿瘤抑制作用，主要取决于癌症的类型。本研究旨在探讨微小 RNA-186（miR-186）在神经胶质瘤中的表达水平及其作用及其潜在的分子机制。采用逆转录-定量聚合酶链反应（RT-qPCR）分析检测神经胶质瘤组织和细胞系中 miR-186 的表达。采用 MTT 和细胞侵袭试验分别评估细胞增殖和侵袭。通过生物信息学分析和荧光素酶报告基因试验鉴定胰岛素样生长因子 1 受体（IGF-1R）为 miR-186 的新型靶基因。采用 RT-qPCR 分析检测 IGF-1R 的 mRNA 表达水平。采用 Spearman 相关分析评估 miR-186 与 IGF-1R 表达的相关性。此外，采用 RT-qPCR 和 Western blot 分析确定 miR-186 对 IGF-1R mRNA 和蛋白表达的调控作用。最后，研究了下调 IGF-1R 对神经胶质瘤细胞的生物学效应。结果表明，miR-186 在神经胶质瘤组织和细胞系中显著下调。诱导 miR-186 的表达抑制神经胶质瘤细胞的增殖和侵袭。IGF-1R 被确认为 miR-186 的直接靶基因。此外，在神经胶质瘤组织中 IGF-1R 的 mRNA 表达上调，与 miR-186 呈负相关。IGF-1R 敲低对神经胶质瘤细胞增殖和侵袭的影响与 miR-186 过表达诱导的影响相似。这些发现表明，miR-186 通过靶向 IGF-1R 在神经胶质瘤中发挥肿瘤抑制作用，提示 miR-186 可能是治疗这种疾病的潜在治疗靶点。
