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

• DOI: 10.1007/s00246-014-0901-y
• Publication Date: 2014-04-08T07:04:14Z
• Authors: Feng Wang; Xue-Yan Yang; Jian-Yuan Zhao; Li-Wei Yu; Ping Zhang; Wen-Yuan Duan; Mei Chong; Yong-Hao Gui
• Keywords: Genetic Markers; Heart Defects, Congenital; Male; 0301 basic medicine; China; 3. Good health; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Humans; Female; Genetic Predisposition to Disease; T-Box Domain Proteins; 3' Untranslated Regions; Protein Processing, Post-Translational

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.