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微小RNA-519d通过直接靶向Smad7促进宫颈癌的进展和转移。

MiR-519d facilitates the progression and metastasis of cervical cancer through direct targeting Smad7.

作者信息

Zhou Jue-Yu, Zheng Si-Rong, Liu Jie, Shi Rong, Yu Hai-Lang, Wei Min

机构信息

Institute of Genetic Engineering, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 Guangdong People's Republic of China.

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 Guangdong People's Republic of China.

出版信息

Cancer Cell Int. 2016 Mar 22;16:21. doi: 10.1186/s12935-016-0298-1. eCollection 2016.

Abstract

BACKGROUND

MicroRNAs (miRNAs) play pivotal roles in the development of various cancer types, including cervical cancer.

METHODS AND RESULTS

In this study, we showed that miR-519d, a miRNA within the chromosome 19 miRNA cluster, was significantly upregulated in cervical cancer tissues, compared with non-tumorous cervical samples. Suppression of miR-519d markedly attenuated the migration and invasion of HeLa and SiHa cervical cancer cells. Additionally, miR-519d inhibited the apoptosis of cervical cancer cells, and the proliferation of cervical cancer cells was also affected following transfection of miR-519d inhibitor. Moreover, we identified Smad7 to be a novel target of miR-519d in cervical cancer cells. MiR-519d matched the 3'-UTR of Smad7 mRNA. Transfection with miR-519d mimics led to apparent downregulation of Smad7 both at the mRNA and protein levels. Luciferase reporter analysis revealed that miR-519d reduced the luciferase activity of Smad7 mRNA 3'-UTR through matching site-dependent manner. And more notably, suppression of Smad7 remarkably restored the migration and invasion of miR-519d-depleted cervical cancer cells.

CONCLUSION

Taken together, these findings implicated that miR-519d promoted the progression and metastasis of cervical cancer through targeting Smad7.

摘要

背景

微小RNA(miRNA)在包括宫颈癌在内的多种癌症类型的发展中起关键作用。

方法与结果

在本研究中,我们发现19号染色体miRNA簇中的miR-519d在宫颈癌组织中显著上调,与非肿瘤性宫颈样本相比。抑制miR-519d显著减弱了HeLa和SiHa宫颈癌细胞的迁移和侵袭。此外,miR-519d抑制宫颈癌细胞的凋亡,转染miR-519d抑制剂后宫颈癌细胞的增殖也受到影响。而且,我们确定Smad7是宫颈癌细胞中miR-519d的一个新靶点。miR-519d与Smad7 mRNA的3'-UTR匹配。转染miR-519d模拟物导致Smad7在mRNA和蛋白质水平上明显下调。荧光素酶报告基因分析表明,miR-519d通过匹配位点依赖的方式降低Smad7 mRNA 3'-UTR的荧光素酶活性。更值得注意的是,抑制Smad7显著恢复了miR-519d缺失的宫颈癌细胞的迁移和侵袭。

结论

综上所述,这些发现表明miR-519d通过靶向Smad7促进宫颈癌的进展和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fffe/4802873/22fef9443bda/12935_2016_298_Fig1_HTML.jpg

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