Down-regulation of miR-106b suppresses the growth of human glioma cells

Down-regulation of miR-106b suppresses the growth of human glioma cells
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miR-106b 的下调抑制人神经胶质瘤细胞的生长

DOI:
10.1007/s11060-013-1061-2
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发表时间:
2013-04-01
影响因子:
3.9
通讯作者:
Pu, Peiyu
Pu, Peiyu
中科院分区:
医学2区
文献类型:
--
作者:
Zhang, Anling;Hao, Jianwei;Pu, Peiyu

文献摘要

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近年来,许多研究发现miR-106 b ~25簇在肿瘤的发生发展中起着致癌作用。然而,每个microRNAs(miRNAs)在簇中的确切作用尚不清楚。在本研究中,我们分别通过实时PCR和原位杂交(ISH)检测了miR-106 b在胶质瘤样本和组织芯片中的表达,发现miR-106 b在大多数胶质瘤中过表达。miR-106 b的表达与肿瘤分级呈正相关(p< 0.05)。将miR-106 b反义寡核苷酸(ASON)转染到3个人脑胶质瘤细胞系(U251、LN 229和TJ 905)中,可抑制这些细胞的增殖。此外,用miR-106 b ASON处理的裸鼠中的异种移植肿瘤的生长显著受损。生物信息学分析预测RBL 2可能是miR-106 b的靶点,双荧光素酶报告基因分析鉴定了RBL 2而不是RB 1或RBL 1作为miR-106 b的靶点。这些结果表明,miR-106 b通过RBL 2的负调控促进细胞周期进程而促进胶质瘤细胞生长。
Recently, many studies have found that the miR-106b ~25 cluster plays an oncogenic role in tumor progression. However, the precise role of each microRNAs (miRNAs) in the cluster is not yet clear. In the present study, we examined the expression of miR-106b in glioma samples and a tissue microarray by real-time PCR and in situ hybridization (ISH), respectively, finding that miR-106b is overexpressed in the majority of gliomas. Meanwhile, the expression of miR-106b was positively correlated with tumor grade (p< 0.05). The transfection of a miR-106b anti-sense oligonucleotide (ASON) into three human glioma cell lines (U251, LN229 and TJ905) suppressed the proliferation of these cells. Moreover, the growth of xenograft tumors in nude mice treated with miR-106b ASON was significantly impaired. A bioinformatics analysis predicted that RBL2 may be the target of miR-106b, and dual-luciferase reporter assays identified RBL2, but not RB1 or RBL1, as a target of miR-106b. These results suggest that miR-106b facilitates glioma cell growth by promoting cell cycle progression through the negative regulation of RBL2.