Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7124-7130. doi: 10.3892/mmr.2017.7433. Epub 2017 Sep 7.
Glioma is the most common and aggressive human brain tumour and accounts for ~35‑61% of intracranial tumours. Despite considerable advances in treatments for glioma, the prognosis for patients with this disease remains unsatisfactory. MicroRNAs (miRNAs of miRs) are small regulatory RNA molecules that have been identified as being involved in the initiation and progression of human cancers, and represent novel therapeutic targets for anticancer treatments. The dysregulation of miR‑188 has been reported in various kinds of human cancer. However, its expression pattern, biological roles and potential mechanism in glioma remain unknown. Expression levels of miR‑188 in glioma tissues and cell lines were detected through reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Cell Counting Kit-8 assays and migration and invasion assays were used to explore the effects of miR‑188 on the proliferation, migration and invasion of glioma cells, respectively. Bioinformatics analysis and luciferase reporter assays were performed to examine insulin‑like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a target gene of miR‑188. RT‑qPCR and Spearman's correlation analysis were then performed to measure IGF2BP2 mRNA expression in clinical glioma tissues and its correlation with miR‑188 expression. The regulatory effect of miR‑188 on IGF2BP2 expression was also investigated through RT‑qPCR and western blotting analysis. Finally, the biological roles of IGF2BP2 in glioma cells were assessed. miR‑188 levels were significantly reduced in glioma tissues and cell lines compared with adjacent normal tissues and normal human astrocytes, respectively. In addition, miR‑188 overexpression suppressed cell proliferation, migration and invasion of glioma. The present study identified IGF2BP2 as a direct target of miR‑188 in glioma, and IGF2BP2 under‑expression served tumour‑suppressive roles in glioma growth and metastasis. Thus, miR‑188 had a similar role in glioma by inhibiting the action of its downstream target, IGF2BP2. Therefore, miR‑188 may be a potential therapeutic target for the prevention and treatment of patients with glioma.
神经胶质瘤是最常见和侵袭性最强的人类脑肿瘤，占颅内肿瘤的~35-61%。尽管神经胶质瘤的治疗取得了相当大的进展，但这种疾病患者的预后仍然不尽人意。微小 RNA（miRNA）是已被确定参与人类癌症发生和进展的小调控 RNA 分子，是癌症治疗的新型治疗靶点。miR-188 的失调已在各种人类癌症中报道。然而，其在神经胶质瘤中的表达模式、生物学作用和潜在机制尚不清楚。通过逆转录-定量聚合酶链反应（RT-qPCR）检测神经胶质瘤组织和细胞系中 miR-188 的表达水平。细胞计数试剂盒-8 检测和迁移及侵袭检测分别用于探索 miR-188 对神经胶质瘤细胞增殖、迁移和侵袭的影响。通过生物信息学分析和荧光素酶报告基因检测实验，检验胰岛素样生长因子 2 mRNA 结合蛋白 2（IGF2BP2）是否为 miR-188 的靶基因。然后进行 RT-qPCR 和 Spearman 相关分析，以检测临床神经胶质瘤组织中 IGF2BP2 mRNA 的表达及其与 miR-188 表达的相关性。还通过 RT-qPCR 和 Western blot 分析研究了 miR-188 对 IGF2BP2 表达的调节作用。最后，评估了 IGF2BP2 在神经胶质瘤细胞中的生物学作用。与相邻正常组织和正常人星形胶质细胞相比，miR-188 在神经胶质瘤组织和细胞系中的水平明显降低。此外，miR-188 过表达抑制了神经胶质瘤细胞的增殖、迁移和侵袭。本研究鉴定 IGF2BP2 是神经胶质瘤中 miR-188 的直接靶基因，IGF2BP2 下调在神经胶质瘤生长和转移中起肿瘤抑制作用。因此，miR-188 通过抑制其下游靶基因 IGF2BP2 的作用在神经胶质瘤中发挥相似作用。因此，miR-188 可能成为预防和治疗神经胶质瘤患者的潜在治疗靶点。
