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微小RNA-132靶向PEA-15并在体外抑制星形细胞瘤的进展。

MicroRNA-132 targets PEA-15 and suppresses the progression of astrocytoma in vitro.

作者信息

Geng Fei, Wu Jian-Lin, Lu Gui-Feng, Liang Zhi-Ping, Duan Zhuo-Li, Gu Xi

机构信息

Department of Neurobiology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.

Guangdong Province Key Laboratory of Neuroplasticity of Guangdong Higher Education Institutes, Guangzhou, 510515, Guangdong, People's Republic of China.

出版信息

J Neurooncol. 2016 Sep;129(2):211-20. doi: 10.1007/s11060-016-2173-2. Epub 2016 Jun 13.

Abstract

Gliomas are highly malignant tumors, the most common of which are astrocytomas. A growing number of studies suggest that dysregulation of miRNAs is a frequent event contributing to the pathogenesis of gliomas. In this study, we found that over-expression of miR-132 inhibited cell proliferation and migration and triggered apoptosis, while knockdown of miR-132 showed opposite effects. PEA-15 was identified as a direct target of miR-132. Reintroduction of PEA-15 without 3'UTR region reversed the inhibitory effects of miR-132 on cell proliferation, migration, and apoptosis. MiR-132 was inversely correlated with the PEA-15 expression. CREB (cAMP response element binding protein) and KLF (Krüppel-like factor 8) were conformed as transcription factors of miR-132, which bidirectionally regulate the expression of miR-132. Our study suggests that miR-132 is an important tumor suppressor of astrocytoma progression by targeting PEA-15, while CREB and KLF can modulate the expression of miR-132, thus providing new insight into the molecular mechanisms underlying astrocytoma progression in vitro.

摘要

胶质瘤是高度恶性肿瘤,其中最常见的是星形细胞瘤。越来越多的研究表明,miRNA失调是导致胶质瘤发病的常见事件。在本研究中,我们发现miR-132的过表达抑制细胞增殖和迁移并引发凋亡,而敲低miR-132则显示出相反的效果。PEA-15被鉴定为miR-132的直接靶点。重新导入不含3'UTR区域的PEA-15可逆转miR-132对细胞增殖、迁移和凋亡的抑制作用。miR-132与PEA-15的表达呈负相关。CREB(cAMP反应元件结合蛋白)和KLF(Krüppel样因子8)被确认为miR-132的转录因子,它们双向调节miR-132的表达。我们的研究表明,miR-132通过靶向PEA-15是星形细胞瘤进展的重要肿瘤抑制因子,而CREB和KLF可以调节miR-132的表达,从而为体外星形细胞瘤进展的分子机制提供了新的见解。

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