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Published on: May 26, 2023
MiR-208a-3p aggravates autophagy through the PDCD4-ATG5 pathway in Ang II-induced H9c2 cardiomyoblasts
Li Wang1, Nan Ye1, Xiaoyu Lian1
1Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai, China.
Insights
MicroRNA-208a-3p promotes autophagy in cardiac hypertrophy by inhibiting PDCD4, offering a potential therapeutic target for heart failure. This study clarifies the link between autophagy dysregulation and cardiac dysfunction.
Area of Science:
- Cardiovascular Biology
- Molecular Cell Biology
- Autophagy Research
Background:
- Pathological cardiac hypertrophy is a key factor in heart failure development with limited therapeutic options.
- Autophagy dysregulation is linked to cardiac hypertrophy, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the regulatory role of microRNA-208a-3p (miR-208a-3p) in autophagy within Angiotensin II (Ang II)-induced H9c2 cardiomyoblasts.
- To elucidate the molecular mechanism connecting miR-208a-3p, autophagy, and cardiac hypertrophy.
Main Methods:
- Induction of cardiac hypertrophy in H9c2 cardiomyoblasts using Angiotensin II (Ang II).
- Analysis of miR-208a-3p expression levels under hypertrophy and starvation-induced autophagy.
- Overexpression and knockdown studies of miR-208a-3p, programmed cell death protein 4 (PDCD4), and autophagy protein 5 (ATG5).
- Dual-luciferase reporter assay to confirm direct binding of miR-208a-3p to PDCD4.
Main Results:
- miR-208a-3p was upregulated in Ang II-induced H9c2 cells and during starvation-induced autophagy.
- Overexpression of miR-208a-3p enhanced Ang II-induced autophagy, inhibited PDCD4, and upregulated ATG5.
- Direct binding between miR-208a-3p and PDCD4 was confirmed.
- PDCD4 modulated autophagy, with knockdown upregulating and overexpression downregulating the process.
- ATG5 was involved in the PDCD4-mediated regulation of autophagy.
Conclusions:
- miR-208a-3p promotes autophagy in the context of Ang II-induced cardiac hypertrophy.
- The miR-208a-3p/PDCD4/ATG5 axis plays a crucial role in regulating autophagy during cardiac hypertrophy.
- These findings offer a potential therapeutic strategy for hypertrophic-induced cardiac dysfunction.
Abstract:
Pathological cardiac hypertrophy is the main determinant of the development of heart failure, for which there is often no effective therapy. The dysregulation of autophagy is implicated in hypertrophy, but the mechanism linking these processes is unclear. In this study, we characterized the regulatory role of miR-208a-3p in autophagy in H9c2 cardiomyoblasts induced by Angiotensin II (Ang II). We found that miR-208a-3p was up-regulated in Ang II-induced H9c2 cardiomyoblasts and in starvation-induced autophagy. The overexpression of miR-208a-3p increased Ang II-induced autophagy, and this was accompanied by the inhibition of programmed cell death protein (PDCD4) and upregulation of autophagy protein 5 (ATG5). A dual-luciferase report assay confirmed the direct binding between miR-208a-3p and PDCD4. PDCD4 knockdown up-regulated autophagy, and its overexpression down-regulated this process. Moreover, the PDCD4-mediated regulation of autophagy was modulated by ATG5. Taken together, these findings indicate that miR-208a-3p promotes autophagy during Ang II-induced hypertrophy and provide a basis for the development of therapies for hypertrophic-induced cardiac dysfunction.
