Li Chuntao, Liu Zhixiong, Yang Kui, Chen Xin, Zeng Yu, Liu Jinfang, Li Zhenyan, Liu Yunsheng
Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, 410008 Hunan, China.
Oncotarget. 2016 Jun 14;7(24):36247-36254. doi: 10.18632/oncotarget.9198.
MicroRNAs (miRs) are a class of small non-coding RNAs that function as mediators of gene expression. Dysregulations of miRs have been implicated in the development and progression of glioma. In the present study, we investigated the role of miR-133b in mediating the proliferation and invasion of glioma cells, and the potential mechanism. Real-time RT-PCR results showed that miR-133b expression was significantly decreased in glioma tissues compared with normal brain tissues. Luciferase reporter assay further identified silent information regulator 1 (Sirt1) as a novel direct target of miR-133b in glioma U87 cells. Overexpression of miR-133b suppressed Sirt1 expression and reduced the proliferation and invasion of U87 cells, which could be partly rescued by forced expression of Sirt1. In addition, the Sirt1 mRNA level was significantly higher in glioma tissues than in normal brain tissues, and was inversely correlated with miR-133b level in glioma tissues. In summary, our study sheds light on the regulatory mechanism of miR-133b in glioma growth and metastasis via direct mediation of Sirt1 expression, and suggests that Sirt1 may serve as a potential therapeutic target for glioma.
微小RNA(miR)是一类小的非编码RNA,作为基因表达的调节因子发挥作用。miR的失调与胶质瘤的发生和发展有关。在本研究中,我们研究了miR-133b在介导胶质瘤细胞增殖和侵袭中的作用及其潜在机制。实时逆转录聚合酶链反应结果显示,与正常脑组织相比,胶质瘤组织中miR-133b的表达显著降低。荧光素酶报告基因检测进一步确定沉默信息调节因子1(Sirt1)是胶质瘤U87细胞中miR-133b的一个新的直接靶点。miR-133b的过表达抑制了Sirt1的表达,并降低了U87细胞的增殖和侵袭,而Sirt1的强制表达可部分挽救这种情况。此外,胶质瘤组织中Sirt1的mRNA水平显著高于正常脑组织,且与胶质瘤组织中miR-133b的水平呈负相关。总之,我们的研究揭示了miR-133b通过直接调节Sirt1的表达在胶质瘤生长和转移中的调控机制,并表明Sirt1可能是胶质瘤的一个潜在治疗靶点。