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miRNA-451 在人神经胶质瘤细胞中作为肿瘤抑制因子发挥作用。

MiRNA-451 plays a role as tumor suppressor in human glioma cells.

机构信息

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, People's Republic of China.

出版信息

Brain Res. 2010 Nov 4;1359:14-21. doi: 10.1016/j.brainres.2010.08.074. Epub 2010 Sep 18.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding loosely complimentary sequences in the 3'untranslated regions (UTRs) of target mRNAs. Increased expressions of several miRNAs, specifically hsa-miR-21, have been reported to modulate glioma development. Here we report downregulation of miR-451 in A172, LN229 and U251 human glioblastoma cells. Increased expression of miR-451 by administration of miR-451 mimics oligonucleotides reversed the biology of each of the three cell lines, inhibiting cell growth, inducing G0/G1 phase arrest and increasing cell apoptosis. Further, treatment with miR-451 mimics oligonucleotides diminished the invasive capacity of these cells, as the number of cells invading through matrigel was significantly decreased. Akt1, CyclinD1, MMP-2, MMP-9 and Bcl-2 protein expression decreased, and p27 expression increased in a dose-dependent manner with miR-451 mimics oligonucleotides. Taken together, these studies reveal miR-451 impacts glioblastoma cell proliferation, invasion and apoptosis, perhaps via regulation of the PI3K/AKT signaling pathway. We propose an essential role for miR-451 as a tumor-suppressor of human glioma.

摘要

微小 RNA(miRNAs)是小的非编码 RNA,可以通过与靶 mRNA 的 3'非翻译区(UTR)中的松散互补序列结合,在转录后和/或翻译水平上负调控基因表达。已经报道了几种 miRNAs(特别是 hsa-miR-21)的表达增加可以调节神经胶质瘤的发展。在这里,我们报告了 miR-451 在 A172、LN229 和 U251 人神经胶质瘤细胞中的下调。通过给予 miR-451 模拟物寡核苷酸增加 miR-451 的表达,逆转了这三种细胞系的生物学特性,抑制细胞生长,诱导 G0/G1 期停滞并增加细胞凋亡。此外,用 miR-451 模拟物寡核苷酸处理可降低这些细胞的侵袭能力,因为穿过基质胶的细胞数量明显减少。Akt1、CyclinD1、MMP-2、MMP-9 和 Bcl-2 蛋白表达呈剂量依赖性降低,而 miR-451 模拟物寡核苷酸则增加了 p27 的表达。总之,这些研究表明 miR-451 影响神经胶质瘤细胞的增殖、侵袭和凋亡,可能通过调节 PI3K/AKT 信号通路。我们提出 miR-451 作为人类神经胶质瘤的肿瘤抑制因子的重要作用。

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