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微小RNA-506通过靶向信号转导和转录激活因子3(STAT3)在胶质瘤中发挥肿瘤抑制作用。

MiR-506 functions as a tumor suppressor in glioma by targeting STAT3.

作者信息

Peng Tao, Zhou Lixiang, Zuo Ling, Luan Yongxin

机构信息

Department of Neurosurgery, First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Department of Ophthalmology, Second Bethune Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

出版信息

Oncol Rep. 2016 Feb;35(2):1057-64. doi: 10.3892/or.2015.4406. Epub 2015 Nov 9.

Abstract

MicroRNA-506 (miR-506) has been reported to act as a tumor suppressive or an oncogenic miRNA in different types of tumors. However, the roles and underlying molecular mechanism of miR-506 in glioma remain unclear. In the present study, we performed quantitative PCR to investigate the level of miR-506 in 36 pairs of glioma tumor and matched adjacent tissues, and found that miR-506 was downregulated in the glioma tumors compared to the expression in the adjacent normal tissues. Furthermore, a functional assay found that ectopic expression of miR-506 in glioma cells markedly suppressed cell proliferation, colony formation, migration and invasion, and suppressed tumor growth in vivo. Moreover, signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-506. Western blot assay showed that overexpression of miR-506 not only induced changes in STAT3 expression but also altered expression of its downstream genes, including, Bcl2, cyclin D1 and matrix metalloproteinase 2 (MMP-2), in the human glioma cells. In addition, STAT3 mRNA expression was increased in the glioma tissues, and was inversely correlated with miR-506. Importantly, overexpression of STAT3 in glioma cells attenuated the suppressive effects of miR-506 on cell proliferation, colony formation, migration and invasion. These results showed that miR-506 functions as a tumor suppressor in glioma by targeting STAT3, suggesting that miR-506 may serve as a potential target in the treatment of human glioma.

摘要

据报道,微小RNA-506(miR-506)在不同类型的肿瘤中可作为肿瘤抑制性或致癌性微小RNA发挥作用。然而,miR-506在胶质瘤中的作用及潜在分子机制仍不清楚。在本研究中,我们进行了定量PCR以检测36对胶质瘤肿瘤组织及其配对的相邻组织中miR-506的水平,发现与相邻正常组织中的表达相比,miR-506在胶质瘤肿瘤中表达下调。此外,功能分析发现,在胶质瘤细胞中异位表达miR-506可显著抑制细胞增殖、集落形成、迁移和侵袭,并在体内抑制肿瘤生长。此外,信号转导和转录激活因子3(STAT3)被确定为miR-506的直接靶点。蛋白质免疫印迹分析表明,miR-506的过表达不仅诱导了人胶质瘤细胞中STAT3表达的变化,还改变了其下游基因包括Bcl2、细胞周期蛋白D1和基质金属蛋白酶2(MMP-2)的表达。此外,STAT3 mRNA在胶质瘤组织中的表达增加,且与miR-506呈负相关。重要的是,在胶质瘤细胞中过表达STAT3可减弱miR-506对细胞增殖、集落形成、迁移和侵袭的抑制作用。这些结果表明,miR-506通过靶向STAT3在胶质瘤中发挥肿瘤抑制作用,提示miR-506可能成为人类胶质瘤治疗的潜在靶点。

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