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MicroRNA-138 通过靶向 CREB1 抑制 AKT/mTOR 信号通路调节神经胶质瘤细胞的生长、凋亡和侵袭。

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1.

机构信息

Department of Neurosurgery, Changzheng Hospital, Navy Medical University, Shanghai 200003, P.R. China.

Department of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China.

出版信息

Oncol Rep. 2020 Dec;44(6):2559-2568. doi: 10.3892/or.2020.7809. Epub 2020 Oct 15.

Abstract

Alterations in the expression of microRNA (miR)‑138 have been demonstrated to result in the development of several malignant tumours. However, the possible function of miR‑138 in human glioma cells remains unclear. The present study demonstrated that miR‑138 was significantly downregulated in 48 human glioma specimens by quantitative PCR analysis. The upregulation of miR‑138 exerted significant antiproliferative and anti‑invasive effects on glioma cells and promoted their apoptosis. In addition, cAMP response element‑binding protein 1 (CREB1) was confirmed as a direct target gene of miR‑138 by luciferase gene reporter assay, and the antitumour effect of miR‑138 on glioma cells was significantly reversed by CREB1 overexpression. Moreover, the molecular mechanisms underlying the tumour‑suppressive role of miR‑138 in malignant glioma may be associated with the dephosphorylation of AKT/mTOR caused by the miR‑138 upregulation‑induced decrease in CREB1 expression in glioma cells. The results of the present study indicated that miR‑138 may affect CREB1/AKT/mTOR signalling to regulate the proliferation, apoptosis and invasion of glioma cells and the malignant progression of glioma, thereby suggesting that miR‑138 may be a potential target for the treatment of gliomas.

摘要

miR-138 的表达改变已被证明可导致几种恶性肿瘤的发生。然而,miR-138 在人神经胶质瘤细胞中的可能功能仍不清楚。本研究通过定量 PCR 分析证实 miR-138 在 48 个人神经胶质瘤标本中显著下调。miR-138 的上调对神经胶质瘤细胞表现出显著的抗增殖和抗侵袭作用,并促进其凋亡。此外,通过荧光素酶基因报告基因检测证实 cAMP 反应元件结合蛋白 1 (CREB1) 是 miR-138 的直接靶基因,并且 CREB1 的过表达显著逆转了 miR-138 对神经胶质瘤细胞的抗肿瘤作用。此外,miR-138 在恶性神经胶质瘤中抑制肿瘤的分子机制可能与 miR-138 上调诱导的 CREB1 表达降低导致 AKT/mTOR 的去磷酸化有关。本研究结果表明,miR-138 可能通过影响 CREB1/AKT/mTOR 信号通路来调节神经胶质瘤细胞的增殖、凋亡和侵袭以及神经胶质瘤的恶性进展,从而提示 miR-138 可能是治疗神经胶质瘤的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e268/7640360/88e487df0dfa/OR-44-06-2559-g00.jpg

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