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miR-146a-5p Mediates Intermittent Hypoxia-Induced Injury in H9c2 Cells by Targeting XIAP
Guofu Lin1, Jiefeng Huang1, Qingshi Chen1,2
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou 350005, China.
Abstract:
MicroRNAs (miRNAs) have emerged as key modulators in the pathophysiologic processes of cardiovascular diseases. However, its function in cardiac injury induced by obstructive sleep apnea (OSA) remains unknown. The aim of the current study was to identify the effect and potential molecular mechanism of miR-146a-5p in intermittent hypoxia(IH)- induced myocardial damage. We exposed H9c2 cells to IH condition; the expression levels of miR-146a-5p were detected by RT-qPCR. Cell viability, cell apoptosis, and the expressions of apoptosis-associated proteins were assessed via Cell Counting Kit-8 (CCK-8), flow cytometry, and western blotting, respectively. Target genes of miR-146a-5p were confirmed by dual-luciferase reporter assay. IH remarkably lowered viability but enhanced cell apoptosis. Concomitantly, the miR-146a-5p expression level was increased in H9c2 cells after IH. Subsequent experiments showed that IH-induced injury was alleviated through miR-146a-5p silence. X-linked inhibitor of apoptosis protein (XIAP) was predicted by bioinformatics analysis and further confirmed as a direct target gene of miR-146a-5p. Surprisingly, the effect of miR-146a-5p inhibition under IH may be reversed by downregulating XIAP expression. In conclusion, our results demonstrated that miR-146a-5p could attenuate viability and promote the apoptosis of H9c2 by targeting XIAP, thus aggravating the H9c2 cell injury induced by IH, which could enhance our understanding of the mechanisms for OSA-associated cardiac injury.
Insights
MicroRNA-146a-5p aggravates cardiac injury from obstructive sleep apnea by targeting XIAP. Inhibiting miR-146a-5p protects heart cells from intermittent hypoxia damage.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Sleep Medicine
Background:
- MicroRNAs (miRNAs) are crucial in cardiovascular disease pathogenesis.
- The role of miRNAs in cardiac injury linked to obstructive sleep apnea (OSA) is largely unexplored.
Purpose of the Study:
- To investigate the role and mechanism of miR-146a-5p in intermittent hypoxia (IH)-induced myocardial damage.
- To identify potential molecular targets of miR-146a-5p in this context.
Main Methods:
- H9c2 cells were subjected to IH conditions.
- miR-146a-5p expression was quantified using RT-qPCR.
- Cell viability, apoptosis, and protein expression were assessed (CCK-8, flow cytometry, Western blotting).
- Dual-luciferase reporter assays confirmed target genes.
Main Results:
- IH significantly reduced cell viability and increased apoptosis in H9c2 cells.
- miR-146a-5p expression was upregulated under IH.
- Inhibition of miR-146a-5p mitigated IH-induced cell injury.
- X-linked inhibitor of apoptosis protein (XIAP) was identified as a direct target of miR-146a-5p.
- Downregulating XIAP reversed the protective effects of miR-146a-5p inhibition.
Conclusions:
- miR-146a-5p exacerbates IH-induced myocardial damage by targeting XIAP, leading to reduced cell viability and increased apoptosis.
- This finding elucidates a key mechanism underlying cardiac injury in OSA.
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