Department of Neurosurgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China.
Department of Oncology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China.
Mol Med Rep. 2019 Jan;19(1):734-742. doi: 10.3892/mmr.2018.9630. Epub 2018 Nov 7.
MicroRNA‑940 (miR‑940) has been extensively studied in the pathogenesis of numerous types of human cancer; however, the expression pattern, roles and molecular mechanisms underlying the regulatory actions of miR‑940 in glioma remain unknown. The present study aimed to further investigate miR‑940 by studying its expression, roles and mechanisms of action in glioma. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect miR‑940 expression in glioma tissues and cell lines. The regulatory effects of miR‑940 in glioma cell proliferation and invasion were determined using MTT and cell invasion assays. Bioinformatics analyses was performed to identify the potential target of miR‑940, which was further confirmed by luciferase reporter assay, RT‑qPCR and western blot analysis. In the present study, significantly increased miR‑940 expression levels were observed in glioma tissues and cell lines compared with normal brain tissues and normal human astrocytes, respectively. Decreased miR‑940 expression levels attenuated glioma cell proliferation and invasion in vitro. Kruppel‑like factor 9 (KLF9) was predicted as a potential target of miR‑940. Further assays demonstrated that miR‑940 negatively regulated KLF9 expression in glioma cells by directly targeting the 3'‑untranslated regions of KLF9. Additionally, KLF9 expression was downregulated in glioma tissues and was inversely correlated with miR‑940. Furthermore, KLF9 knockdown was able to rescue the effects of miR‑940 on glioma cell proliferation and invasion. The results of the present study suggest that miR‑940 may function as an oncogene in glioma by targeting KLF9 and may be a considered a therapeutic target for the treatment of gliomas.
微小 RNA-940（miR-940）在多种人类癌症的发病机制中得到了广泛研究；然而，miR-940 在神经胶质瘤中的表达模式、作用和调控机制仍不清楚。本研究旨在通过研究 miR-940 在神经胶质瘤中的表达、作用和作用机制，进一步研究 miR-940。逆转录-定量聚合酶链反应（RT-qPCR）用于检测神经胶质瘤组织和细胞系中 miR-940 的表达。通过 MTT 和细胞侵袭实验检测 miR-940 对神经胶质瘤细胞增殖和侵袭的调控作用。采用生物信息学分析鉴定 miR-940 的潜在靶标，进一步通过荧光素酶报告基因检测、RT-qPCR 和 Western blot 分析进行验证。在本研究中，与正常脑组织和正常星形胶质细胞相比，神经胶质瘤组织和细胞系中 miR-940 的表达水平显著升高。降低 miR-940 的表达水平可减弱神经胶质瘤细胞在体外的增殖和侵袭能力。Krüppel 样因子 9（KLF9）被预测为 miR-940 的潜在靶标。进一步的实验表明，miR-940 通过直接靶向 KLF9 的 3'UTR 负调控神经胶质瘤细胞中的 KLF9 表达。此外，KLF9 在神经胶质瘤组织中的表达下调，且与 miR-940 呈负相关。此外，KLF9 敲低能够挽救 miR-940 对神经胶质瘤细胞增殖和侵袭的影响。本研究结果表明，miR-940 可能通过靶向 KLF9 作为神经胶质瘤的致癌基因发挥作用，并且可以作为治疗神经胶质瘤的潜在治疗靶点。
