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Published on: July 10, 2019
CircRbms1 knockdown alleviates hypoxia-induced cardiomyocyte injury via regulating the miR-742-3p/FOXO1 axis
1Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No.1665 Kongjiang Road, 20092, Shanghai, China.
Insights
Circular RNA circRbms1 exacerbates myocardial infarction (MI) by sponging miR-742-3p and upregulating FOXO1, leading to cardiomyocyte injury. Targeting circRbms1 may offer a novel therapeutic strategy for MI treatment.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in cardiovascular diseases like myocardial infarction (MI).
- The specific role of circRbms1 in MI pathogenesis was previously unclear.
Purpose of the Study:
- To investigate the function and mechanism of circRbms1 in myocardial infarction.
- To explore the regulatory relationship between circRbms1, miR-742-3p, and FOXO1 in cardiomyocyte injury.
Main Methods:
- Constructed in vivo MI mouse models and in vitro hypoxia-induced cardiomyocyte injury models.
- Quantified expression of circRbms1, miR-742-3p, and FOXO1 using qRT-PCR.
- Assessed cell viability, migration, invasion, and apoptosis via CCK-8, Transwell, and flow cytometry assays.
- Verified molecular interactions using dual-luciferase reporter, RNA pull-down, and RIP assays.
Main Results:
- CircRbms1 expression was elevated in MI heart tissues and hypoxia-treated cardiomyocytes.
- CircRbms1 overexpression worsened hypoxia-induced cardiomyocyte injury, while silencing protected against it.
- CircRbms1 acted as a sponge for miR-742-3p, and FOXO1 was identified as a target of miR-742-3p.
- MiR-742-3p alleviated injury, and its effects were modulated by circRbms1 and FOXO1 levels.
Conclusions:
- CircRbms1 promotes hypoxia-induced cardiomyocyte injury by regulating the miR-742-3p/FOXO1 axis.
- CircRbms1 represents a potential therapeutic target for myocardial infarction treatment.
Background:
Circular RNA (circRNA) has been shown to play an important role in a variety of cardiovascular diseases, including myocardial infarction (MI). However, the role of circRbms1 in MI progression remains unclear.
Methods:
An MI mouse model was constructed in vivo, and cardiomyocytes were cultured under hypoxia condition to induce a cardiomyocyte injury model in vitro. The expression levels of circRbms1, microRNA (miR)-742-3p, and forkhead box O1 (FOXO1) were determined by quantitative real-time PCR. Cell viability, migration, invasion, and apoptosis were measured using Cell Counting Kit-8 assay, transwell assay, and flow cytometry. Meanwhile, western blot analysis was used to examine the protein levels of apoptosis markers and FOXO1. Additionally, dual-luciferase reporter assay, RNA pull-down assay, and RIP assay were employed to verify the interactions between miR-742-3p and circRbms1 or FOXO1.
Results:
CircRbms1 was upregulated in the heart tissues of MI mice and hypoxia-induced cardiomyocytes. Hypoxia induced cardiomyocyte injury by suppressing cell viability, migration, and invasion, and promoting apoptosis. Function experiments showed that circRbms1 overexpression aggravated hypoxia-induced cardiomyocyte injury, while its silencing relieved cardiomyocyte injury induced by hypoxia. Furthermore, circRbms1 sponged miR-742-3p. MiR-742-3p overexpression alleviated hypoxia-induced cardiomyocyte injury, and its inhibitor reversed the suppressive effect of circRbms1 silencing on hypoxia-induced cardiomyocyte injury. Further experiments showed that FOXO1 was a target of miR-742-3p, and its expression was positively regulated by circRbms1. The inhibitory effect of miR-742-3p on hypoxia-induced cardiomyocyte injury was reversed by FOXO1 overexpression.
Conclusion:
CircRbms1 regulated the miR-742-3p/FOXO1 axis to mediate hypoxia-induced cardiomyocyte injury, suggesting that circRbms1 might be an effective target for MI treatment.
