期刊
MOLECULAR MEDICINE REPORTS
卷 14, 期 3, 页码 2860-2866出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2016.5574
关键词
cardiac hypertrophy; microRNA-26a; GATA4; cardiomyocyte
Pathological cardiac hypertrophy is characterized by deleterious changes developed in cardiovascular diseases, whereas microRNAs (miRNAs) are involved in the mediation of cardiac hypertrophy. To investigate the role of microRNA-26a (miR-26a) in regulating cardiac hypertrophy and its functioning mechanisms, overexpression and suppression of miR-26a via its mimic and inhibitor in a transverse abdominal aortic constriction (TAAC)-induced rat model and in angiotensin II (Ang II)-induced cardiomyocytes (CMs) was performed. In the rat model, the heart weight (HW) compared with the body weight (BW), the CM area, and expression of the hypertrophy-associated factors, atrial natriuretic factor (ANF) and -myosin heavy chain (-MHC), were assessed. In CMs, the protein synthesis rate was determined using a leucine incorporation assay. Mutation of the GATA-binding protein 4 (GATA4) 3-untranslated region (UTR) and overexpression of GATA4 were performed to confirm whether GATA4 is the target of miR-26a. The results indicated that miR-26a was significantly downregulated in the heart tissue of the rat model, as well as in Ang II-induced CMs (P<0.05). The TAAC-induced rat model exhibited a higher HW/BW ratio, a larger CM area, and higher expression levels of ANF and -MHC. CMs, upon Ang II treatment, also demonstrated a larger CM area, higher levels of ANF and -MHC, as well as accelerated protein synthesis. miR-26a was not able to regulate GATA4 with mutations in the 3-UTR, indicating that GATA4 was the direct target of miR-26a. Overexpression of GATA4 abrogated the inhibitory functions of miR-26a in cardiac hypertrophy. Taken together, the present study suggested an anti-hypertrophic role of miR-26a in cardiac hypertrophy, possibly via inhibition of GATA4. These findings may be useful in terms of facilitating cardiac treatment, with potential therapeutic targets and strategies.
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