CircPAN3/miR-221/PTEN axis and apoptosis in myocardial Infarction: Quercetin's regulatory effects
Mohammad Mojtaba Farazi1, Farzaneh Rostamzadeh2, Saeideh Jafarinejad-Farsangi3
1Department of Biology, Faculty of Science, Shahid Bahonar University of Kerman, Kerman, Iran.
Abstract:
The circular RNA/microRNA/mRNA axis is a new layer of non-coding RNA(ncRNA)-based regulatory gene expression networks upstream of numerous cell signaling pathways. Circular RNAPAN3 (circPAN3) is involved in autophagy, fibrosis and apoptosis which are responsible for the reduction incardiac functional capacityfollowingmyocardial infarction(MI). However, the molecular mechanism of circPAN3 association with apoptosis is unknown. In addition, the relationship between quercetin as a cardioprotective factor in MI and circular RNA-dependent regulatory pathways has not yet been elucidated. MI was induced in Wistar rats using the left anterior descending artery (LAD) ligation method. One day after surgery, quercetin (30 mg/kg) was injected intraperitoneal (IP) every other day for two weeks. The expression of circPAN3 was increased in the MI group (P < 0.05). The increase in circPAN3 was accompanied by a decrease in miR-221 (P < 0.0001), an increase in PTEN (P < 0.0001), and cleaved caspase 3 (P < 0.001). Quercetin effectively reduced the expression of circPAN3 (P < 0.05), PTEN (P < 0.0001), and cleaved caspase 3 (P < 0.001), and increased the expression of miR-221 (P < 0.0001) and the ratio of p-AKT to p-PI3K (P < 0.001). The circPAN3/miR-221/PTEN pathway is an ncRNA-dependent apoptotic pathway in MI cardiac tissue. Quercetin effectively modulated this pathway, resulting in a reduction of cardiac tissue death and improvement in cardiac function after MI. This suggests that the circPAN3/miR-221 axis plays a role in apoptosis in MI, and quercetin can act as a protective candidate by modulating this pathway.
Insights
Circular RNA PAN3 (circPAN3) promotes apoptosis in myocardial infarction (MI) by regulating the miR-221/PTEN pathway. The cardioprotective compound quercetin effectively modulates this circPAN3/miR-221 axis, reducing cardiac cell death and improving heart function post-MI.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Non-coding RNA Biology
Background:
- The circular RNA/microRNA/mRNA axis represents a novel regulatory layer in gene expression.
- Circular RNAPAN3 (circPAN3) is implicated in processes like apoptosis, crucial in myocardial infarction (MI).
- The specific molecular mechanisms of circPAN3 in MI-induced apoptosis and the role of quercetin remain unclear.
Purpose of the Study:
- To investigate the molecular mechanism of circPAN3 in apoptosis following myocardial infarction.
- To explore the relationship between the cardioprotective agent quercetin and circular RNA-dependent pathways in MI.
- To elucidate the circPAN3/miR-221/PTEN pathway in MI cardiac tissue.
Main Methods:
- Myocardial infarction was induced in Wistar rats via LAD ligation.
- Quercetin treatment (30 mg/kg) was administered intraperitoneally every other day for two weeks post-MI.
- Expression levels of circPAN3, miR-221, PTEN, cleaved caspase 3, p-AKT, and p-PI3K were analyzed.
Main Results:
- MI significantly increased circPAN3 expression, decreased miR-221, and increased PTEN and cleaved caspase 3.
- Quercetin treatment reversed these changes, reducing circPAN3, PTEN, and cleaved caspase 3, while increasing miR-221 and the p-AKT/p-PI3K ratio.
- The circPAN3/miR-221/PTEN pathway was identified as an ncRNA-dependent apoptotic pathway in MI cardiac tissue.
Conclusions:
- The circPAN3/miR-221 axis plays a significant role in apoptosis during myocardial infarction.
- Quercetin demonstrates cardioprotective effects in MI by modulating the circPAN3/miR-221/PTEN pathway.
- Targeting this pathway offers a potential therapeutic strategy for improving cardiac function after MI.
