Aim
Although miR-29 has emerged as a crucial non-coding RNA in the regulation of pathological cardiac hypertrophy, further exploration of its specific mechanisms is necessary to resolve controversy about its major role in this condition. This study therefore evaluated the role of miR-29a and whether it acts through the PTEN/AKT/mTOR pathway.
Conclusion
In pathological cardiac hypertrophy, miR-29a was overexpressed and promoted cardiac hypertrophy by regulating the PTEN/AKT/mTOR pathway and suppressing autophagy.
Methods
In this study, a rat model of pressure-induced cardiac hypertrophy was established by transverse aortic constriction and verified by echocardiography, histological analysis and quantitative RT-PCR. At the cellular level, we explored the role of miR-29a in angiotensin II-stimulated hypertrophic H9c2 cardiomyoblasts by transfecting the cells with miR-29a inhibitor and mimic. The relationship between miR-29a and the signalling pathway was investigated with dual luciferase reporter assays, immunofluorescence analysis and Western blotting. We also examined whether autophagy is involved in the regulatory mechanism of miR-29a through transmission electron microscopy and detection of autophagy-associated proteins.
Results
The results showed that miR-29a was upregulated both in rats 4 weeks after surgery and in 10-6 M angiotensin II-stimulated cells. In contrast, inhibition of miR-29a partially attenuated angiotensin II-induced hypertrophy. Additionally, bioinformatics analysis revealed that PTEN was one of the target genes of miR-29a, which was also verified by luciferase assay. The results of immunofluorescence and Western blotting indicated that overexpression of miR-29a inhibited the expression of PTEN, activated the AKT/mTOR pathway and suppressed autophagy, which ultimately led to cardiac hypertrophy.