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MiR-149 Aggravates Pyroptosis in Myocardial Ischemia-Reperfusion Damage via Silencing FoxO3
Jie Lin1, Haihuan Lin2, Chao Ma3
1Department of Cardiology, Shenzhen University General Hospital, Shenzhen, Guandong, China (mainland).
Abstract:
BACKGROUND MicroRNAs (miRNAs), which modulate the expression of their target genes, are commonly involved in stimulating and adjusting of many processes that result in cardiovascular diseases, contain cardiac ischemia/reperfusion (I/R) damage. However, the expression and role of miR-149 in pyroptosis mediated myocardial I/R damage remains unclear. MATERIAL AND METHODS Real-time polymerase chain reaction was performed to measure the miR-149 and FoxO3 expression in I/R stimulated H9C2 cells. The cell proliferation, pyroptosis-related inflammatory genes in I/R-treated H9C2 cells transfected miR-149 mimics or miR-149 inhibitor were both explored. We predicted and confirmed miR-149 targets by using bioinformatics analyses and luciferase reporter assay. In addition, the potential relationship between miR-149 and FoxO3 in pyroptosis from I/R treated H9C2 cells was analyzed. RESULTS Our results showed that miR-149 was upregulated, while FoxO3 was downregulated in I/R stimulated H9C2 cells. Over-expression of miR-149 inhibited cell viability and promote pyroptosis, however, down-expression of miR-149 had an opposite effect in I/R treated H9C2 cells. Furthermore, miR-149 could negatively regulate FoxO3 expression by binding 3'UTR, whereas silencing of FoxO3 attenuated the effect of miR-149-mimics on cell proliferation and pyroptosis in I/R treated H9C2 cells. CONCLUSIONS Our study found that miR-149 played a critical role in pyroptosis during cardiac I/R injury, and thus, might provide a novel therapeutic target.
Insights
MicroRNA-149 (miR-149) promotes pyroptosis in cardiac ischemia/reperfusion (I/R) injury by downregulating FoxO3. This finding identifies miR-149 as a potential therapeutic target for heart damage.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cellular Signaling
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in cardiovascular diseases.
- Cardiac ischemia/reperfusion (I/R) injury involves complex cellular processes.
- The specific role of miR-149 in pyroptosis during myocardial I/R injury was previously unknown.
Purpose of the Study:
- To investigate the expression and function of miR-149 in pyroptosis-mediated myocardial I/R damage.
- To elucidate the regulatory relationship between miR-149 and FoxO3 in this context.
Main Methods:
- Quantitative real-time PCR to measure miR-149 and FoxO3 levels in I/R-stimulated H9C2 cells.
- Transfection with miR-149 mimics or inhibitors to assess effects on cell viability and pyroptosis.
- Bioinformatics analysis and luciferase reporter assays to confirm miR-149 targets.
- Analysis of the interplay between miR-149 and FoxO3 in I/R-treated cells.
Main Results:
- miR-149 was upregulated, and FoxO3 was downregulated in I/R-stimulated H9C2 cells.
- Overexpression of miR-149 enhanced cell pyroptosis and inhibited viability, while downregulation had opposite effects.
- miR-149 directly targets and downregulates FoxO3 expression.
- Silencing FoxO3 partially reversed the effects of miR-149 overexpression on cell proliferation and pyroptosis.
Conclusions:
- miR-149 plays a significant role in promoting pyroptosis during cardiac I/R injury.
- The miR-149/FoxO3 axis is a key pathway in myocardial I/R damage.
- miR-149 represents a potential novel therapeutic target for mitigating cardiac I/R injury.
