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Suppression of microRNA-142-5p attenuates hypoxia-induced apoptosis through targeting SIRT7
Liying Zhan1, Shaoqing Lei1, Wenlan Li1
1Department of Anesthesia, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Abstract:
Increasing study has suggested that microRNAs (miRNAs) are pivotal regulators in regulating hypoxia-induced injury. miR-142-5p has been suggested as a critical regulator for cellular survival. However, the role of miR-142-5p in regulating hypoxia-induced injury remains unknown. In this study, we aimed to investigate the mechanistic roles of miR-142-5p in regulating cell survival during hypoxia treatment using H9C2 cardiomyoblasts and primary cardiomyocytes. We showed that miR-142-5p expression level was significantly repressed by hypoxia treatment. Overexpression of miR-142-5p during hypoxia induced extensive cell injury and apoptosis whereas suppression of miR-142-5p significantly promoted cell viability and attenuated cell apoptosis with hypoxia treatment. Sirtuin7 (SIRT7) was identified as a direct target gene of miR-142-5p by bioinformatics analysis and dual-luciferase reporter assays. Overexpression of miR-142-5p significantly decreased SIRT7 expression, while suppression of miR-142-5p increased SIRT7 expression. Furthermore, overexpression of SIRT7 protected H9C2 cardiomyoblasts and primary cardiomyocytes against hypoxia-induced injury and apoptosis. The silencing of SIRT7 markedly abrogated the protective effect induced by miR-142-5p suppression. Taken together, these results suggest that downregulation of miR-142-5p alleviates hypoxia-induced injury through upregulation of SIRT7. Our study suggests miR-142-5p/SIRT7 as potential therapeutic targets for ischemic heart disease.
Insights
Downregulating microRNA-142-5p (miR-142-5p) protects heart cells from hypoxia-induced injury by increasing Sirtuin7 (SIRT7) expression. This miR-142-5p/SIRT7 pathway offers potential therapeutic targets for ischemic heart disease.
Area of Science:
- Molecular Biology
- Cell Biology
- Cardiovascular Research
Background:
- MicroRNAs (miRNAs) are key regulators of cellular responses to hypoxia.
- miR-142-5p is implicated in cellular survival, but its role in hypoxia-induced injury is unclear.
- Hypoxia-induced injury is a significant factor in cardiovascular diseases.
Purpose of the Study:
- To investigate the role of miR-142-5p in regulating cell survival during hypoxia.
- To elucidate the underlying molecular mechanisms of miR-142-5p in hypoxia-induced injury.
- To identify potential therapeutic targets for mitigating cardiac damage from hypoxia.
Main Methods:
- Utilized H9C2 cardiomyoblasts and primary cardiomyocytes for experiments.
- Manipulated miR-142-5p expression levels (overexpression and suppression) under hypoxia.
- Employed bioinformatics analysis and dual-luciferase reporter assays to identify miR-142-5p targets.
- Assessed cell viability, apoptosis, and gene expression (SIRT7).
Main Results:
- Hypoxia significantly repressed miR-142-5p expression.
- miR-142-5p overexpression exacerbated hypoxia-induced cell injury and apoptosis.
- miR-142-5p suppression promoted cell viability and reduced apoptosis during hypoxia.
- Sirtuin7 (SIRT7) was identified as a direct target of miR-142-5p, with inverse expression correlation.
- SIRT7 overexpression protected cells against hypoxia-induced injury, while SIRT7 silencing abrogated the protective effects of miR-142-5p suppression.
Conclusions:
- Downregulation of miR-142-5p alleviates hypoxia-induced injury in cardiomyocytes by upregulating SIRT7.
- The miR-142-5p/SIRT7 axis represents a promising therapeutic target for ischemic heart disease.
- Understanding this regulatory pathway can lead to novel strategies for treating conditions involving cardiac hypoxia.
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