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

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.

Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease

“…Rather than acting independently of one another, these systems act in an integrated fashion to regulate cardiac gene expression in a coordinated manner. In fact, several cardiac-expressed miRNAs were found to be involved in the TBX5 [114,121], GATA-4 [122][123][124][125][126], SRF/MYOCD [124,126,127], and PITX2 [97] regulatory network in settings of cardiovascular disease. There is evidence that circulating miRNAs may be used as biomarkers for patients with HFpEF, but their expression has not yet been assessed in the diastolic heart [128].…”

Circulating microRNAs as potential biomarkers for diagnosis of congenital heart defects

“…Results showed that the average levels of miR-10a and miR-10b in heart tissue of CHD (n=28) were as approximately 3-fold high as those in controls (n=9). [27] However, the subtypes of heart defects were not specified in this study. A stratification analysis on the expression levels of miR-10a and miR-10b in terms of the subtypes of heart defects would be of more pathobiological signifi cance.…”

“…Wang et al [27] 28 CHD samples (4 atrium, 3 ventricle, 1 auricle, 2 ventricular septum, 10 outlet, and 8 aorta samples) versus 9 normal heart tissue samples qRT-PCR miR-10a, miR-10b…”

“…Moreover, they showed that the decrease of miR-1-1 expression was associated with the increased levels of GJA1 and SOX9, and that the increased miR-181c expression was linked with the down-regulation of BMPR2 in VSD samples. [26] MiR-10a and miR-10b in CHD Wang et al [27] first found that TBX5, which is a key transcription factor playing a role in heart development, was a target gene of both miR-10a and miR-10b. This finding encouraged them to determine the miR-10a and miR-10b expression levels in heart tissues of CHD relative to healthy controls.…”

Emerging Biomarkers of Congenital Heart Diseases and Disorders

“…Similarly, levels of norepinephrine found altered in symptomatic patients, especially those with unrepaired congenital heart disease, Eisenmenger syndrome, pulmonary hypertension and adult congenital heart failure [38]. These are used as, molecular markers for prediction of congenital heart disease [39]. Similarly, level ofTBX5 a transcription factor diagnose embryonic cardiac defects [40].…”