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MicroRNA-3666 通过靶向 KDM2A 抑制胶质母细胞瘤细胞的生长和迁移。

MicroRNA‑3666 suppresses the growth and migration of glioblastoma cells by targeting KDM2A.

机构信息

Department of Neurosurgery, The Affiliated Huai'an No. 1 Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.

出版信息

Mol Med Rep. 2019 Feb;19(2):1049-1055. doi: 10.3892/mmr.2018.9698. Epub 2018 Nov 27.

Abstract

MicroRNAs (miRNAs) are acknowledged as essential regulators in human cancer types, including glioblastoma (GBM). However, the functions of microRNA‑3666 (miR‑3666) in GBM remain unclear. In the present study, it was identified that the expression of miR‑3666 was significantly downregulated in GBM tissues compared with adjacent normal tissues by reverse transcription‑quantitative polymerase chain reaction. Additionally, miR‑3666 was downregulated in GBM cell lines. Furthermore, it was observed that the miR‑3666 expression level in patients with GBM was associated with prognosis. With functional experiments, it was identified that overexpression of miR‑3666 significantly inhibited the proliferation, migration and invasion of GBM cells in vitro by Cell Counting kit‑8 and Transwell assays. Ectopic expression of miR‑3666 significantly arrested GBM cells in the G0 phase by fluorescence activated cell sorting. In terms of the underlying mechanism, it was identified that lysine‑specific demethylase 2A (KDM2A) is a direct target of miR‑3666 in GBM cells. Overexpression of miR‑3666 significantly decreased the expression of KDM2A in GBM cells. Furthermore, it was observed that knockdown of KDM2A significantly suppressed the proliferation, migration and invasion of GBM cells. Collectively, the present results demonstrated that the miR‑3666/KDM2A axis serves an important role in the progression of GBM, which provides novel insight into the development of therapeutic strategies for GBM treatment.

摘要

微小 RNA(miRNA)被认为是包括神经胶质瘤(GBM)在内的多种人类癌症类型的重要调控因子。然而,miRNA-3666(miR-3666)在 GBM 中的功能仍不清楚。在本研究中,通过逆转录-定量聚合酶链反应(RT-qPCR)发现,miR-3666 在 GBM 组织中的表达明显低于相邻正常组织。此外,在 GBM 细胞系中也下调了 miR-3666 的表达。此外,还观察到 GBM 患者的 miR-3666 表达水平与预后相关。通过功能实验,通过细胞计数试剂盒-8 和 Transwell 分析发现,miR-3666 的过表达可显著抑制 GBM 细胞在体外的增殖、迁移和侵袭。荧光激活细胞分选(FACS)表明,miR-3666 的异位表达可使 GBM 细胞明显停滞在 G0 期。在潜在机制方面,发现赖氨酸特异性去甲基化酶 2A(KDM2A)是 GBM 细胞中 miR-3666 的直接靶标。miR-3666 的过表达可显著降低 GBM 细胞中 KDM2A 的表达。此外,还观察到 KDM2A 的敲低可显著抑制 GBM 细胞的增殖、迁移和侵袭。综上所述,本研究结果表明,miR-3666/KDM2A 轴在 GBM 的进展中发挥着重要作用,为 GBM 治疗的治疗策略的开发提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38de/6323202/9d5dcff0abc6/MMR-19-02-1049-g00.jpg

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