MicroRNA-7 inhibits the growth of human non-small cell lung cancer A549 cells through targeting BCL-2.

MicroRNA-7 inhibits the growth of human non-small cell lung cancer A549 cells through targeting BCL-2.
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MicroRNA-7 通过靶向 BCL-2 抑制人非小细胞肺癌 A549 细胞的生长

DOI:
10.7150/ijbs.7.805
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发表时间:
2011
影响因子:
9.2
通讯作者:
Chu Y
Chu Y
中科院分区:
生物学2区
文献类型:
--
作者:
Xiong S;Zheng Y;Jiang P;Liu R;Liu X;Chu Y

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MicroRNAs(miRNAs)在肿瘤发生中逐渐成为重要的调节因子。越来越多的证据表明,microRNA-7(miR-7)在几种人类癌症中是一种潜在的肿瘤抑制因子。然而,目前发现的靶基因数量有限,其在非小细胞肺癌(Non-Small Cell Lung Cancer, NSCLC)中的生物学功能有待进一步阐明。在本研究中,我们观察到在NSCLC细胞系中miR-7水平的降低。过表达miR-7不仅在体外抑制NSCLC A549细胞增殖、诱导细胞凋亡、抑制细胞迁移,而且在体内降低致瘤性。生物信息学预测揭示了miR-7在BCL-2的3'UTR上的潜在结合位点,并通过荧光素酶试验进一步证实了这一点。此外,随后的实验表明,miR-7在转录和翻译水平上下调BCL-2。这些结果表明,miR-7通过直接3'UTR相互作用调节BCL-2的表达。因此,我们推测BCL-2可能是参与mir -7介导的A549细胞生长抑制和凋亡的新靶点。这些发现可能为使用miR-7治疗非小细胞肺癌提供了基本的理论依据。
MicroRNAs(miRNAs) are emerging as important regulators in tumorigenesis. Increasing evidences have indicated microRNA-7(miR-7) to be a potential tumor suppressor in several human cancers. However, only a limited number of target genes have been identified so far and its biological function in Non-Small Cell Lung Cancer (NSCLC) remains to be further elucidated. In the present study, we observed a reduction of miR-7 level in NSCLC cell lines. Overexpression of miR-7 not only suppressed NSCLC A549 cells proliferation, induced cell apoptosis and inhibited cell migration in vitro, but also reduced tumorigenicity in vivo. Bioinformatics predictions revealed a potential binding site of miR-7 on 3'UTR of BCL-2 and it was further confirmed by luciferase assay. Moreover, subsequent experiments showed that BCL-2 was downregulated by miR-7 at both transcriptional and translational levels. These results suggest that miR-7 regulates the expression of BCL-2 through direct 3'UTR interactions. Therefore, we postulate BCL-2 to be a novel target possibly involved in miR-7-mediated growth suppression and apoptosis of A549 cells. These findings may provide a basic rationale for the use of miR-7 in the treatment of NSCLC.
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发表时间: 2011-01-27
影响因子: 9.2
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