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miR-10a和miR-10b靶向TBX5的3'非翻译区以抑制其表达。

miR-10a and miR-10b target the 3'-untranslated region of TBX5 to repress its expression.

作者信息

Wang Feng, Yang Xue-Yan, Zhao Jian-Yuan, Yu Li-Wei, Zhang Ping, Duan Wen-Yuan, Chong Mei, Gui Yong-Hao

机构信息

Department of Cardiology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.

出版信息

Pediatr Cardiol. 2014 Aug;35(6):1072-9. doi: 10.1007/s00246-014-0901-y. Epub 2014 Apr 9.

Abstract

As a well-known transcription factor, TBX5 is involved in embryonic cardiac development. Although TBX5 functions in a dose-dependent manner, the posttranscriptional regulation of human TBX5 is poorly understood. Thus, this study aimed to identify microRNAs that modulate TBX5 expression. Luciferase assays were used to screen miRNAs predicted to modulate TBX5 expression. Using quantitative reverse transcriptase-polymerase chain reaction and Western blot analysis, the authors found that miR-10a and miR-10b significantly repressed TBX5 expression and decreased TBX5 protein levels by targeting the TBX5 3'-untranslated region. In addition, miR-10a and miR-10b expression levels were respectively 2.77 and 3.51 times higher in the heart tissues of congenital heart disease patients than in healthy control subjects, suggesting that they are potential diagnostic biomarkers. In conclusion, the study results indicate that miR-10a and miR-10b inhibit TBX5 expression at the level of translation. Higher levels of miR-10a and miR-10b expression are associated with a higher risk of congenital heart defects.

摘要

作为一种著名的转录因子,TBX5参与胚胎心脏发育。尽管TBX5以剂量依赖的方式发挥作用,但对人类TBX5的转录后调控了解甚少。因此,本研究旨在鉴定调节TBX5表达的微小RNA。荧光素酶测定法用于筛选预测可调节TBX5表达的微小RNA。通过定量逆转录聚合酶链反应和蛋白质印迹分析,作者发现miR-10a和miR-10b通过靶向TBX5的3'非翻译区显著抑制TBX5表达并降低TBX5蛋白水平。此外,先天性心脏病患者心脏组织中miR-10a和miR-10b的表达水平分别比健康对照者高2.77倍和3.51倍,表明它们是潜在的诊断生物标志物。总之,研究结果表明miR-10a和miR-10b在翻译水平上抑制TBX5表达。miR-10a和miR-10b的较高表达水平与先天性心脏缺陷的较高风险相关。

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