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MiR-10a and MiR-10b Target the 3′-Untranslated Region of TBX5 to Repress Its Expression

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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.

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Acknowledgments

We thank Dr. Songshan Jiang for providing miRNAs expression plasmids and Professor Duan Ma for providing the normal heart tissues. This work was supported by the 973 Program (2013CB945401) and grants from the National Science Fund for the National Natural Science Foundation of China (81170147) to Yonghao Gui, grants from the National Science Fund for the National Natural Science Foundation of China (81300126) to Feng Wang, grants from the 973 Program (2012CB944604, 2013CB945300) and the National Natural Science Foundation of China (31000542) to Xueyan Yang, and grants from the National Natural Science Foundation of China (81100116) to Mei Chong.

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Authors and Affiliations

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

    Feng Wang, Li-Wei Yu, Ping Zhang & Yong-Hao Gui

  2. The State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China

    Xue-Yan Yang & Jian-Yuan Zhao

  3. Cardiovascular Disease Institute, General Hospital of Jinan Military Command, Jinan, Shandong, China

    Wen-Yuan Duan

  4. Department of Pediatric Cardiology, AnZhen Hospital, Capital Medical University, Beijing, China

    Mei Chong

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  1. Feng Wang
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Correspondence to Yong-Hao Gui.

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Wang, F., Yang, XY., Zhao, JY. et al. MiR-10a and MiR-10b Target the 3′-Untranslated Region of TBX5 to Repress Its Expression. Pediatr Cardiol 35, 1072–1079 (2014). https://doi.org/10.1007/s00246-014-0901-y

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  • DOI: https://doi.org/10.1007/s00246-014-0901-y

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