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LncRNA A2M-AS1 lessens the injury of cardiomyocytes caused by hypoxia and reoxygenation via regulating IL1R2

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Abstract

Background

Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear.

Objective

To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism.

Methods

Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Human neonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively.

Results

The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1.

Conclusion

This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.

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Data availability

The data in this study is available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Graduate School, Hebei Medical University, Shijiazhuang, 050017, Hebei, People’s Republic of China

    Xue-Lian Song & Xiao-Yong Qi

  2. Department of Cardiology Center, Hebei General Hospital, No. 348 of Heping West Road, Shijiazhuang, 050051, Hebei, People’s Republic of China

    Fei-Fei Zhang, Wen-Jing Wang, Xin-Ning Li, Yi Dang, Ying-Xiao Li, Qian Yang, Mei-Jing Shi & Xiao-Yong Qi

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  1. Xue-Lian Song
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Contributions

XYQ conceived and instructed the work. XNL and YD collected the public data and performed the bioinformatics analysis. XLS,FFZ,WJW and MJS carried out a series of tests. YXL and QY analyzed the experimental data. XLS wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xiao-Yong Qi.

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Xue-Lian Song, Fei-Fei Zhang, Wen-Jing Wang, Xin-Ning Li, Yi Dang, Ying-Xiao Li, Qian Yang, Mei-Jing Shi, and Xiao-Yong Qi declare that they have no conflict of interest.

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Song, XL., Zhang, FF., Wang, WJ. et al. LncRNA A2M-AS1 lessens the injury of cardiomyocytes caused by hypoxia and reoxygenation via regulating IL1R2. Genes Genom 42, 1431–1441 (2020). https://doi.org/10.1007/s13258-020-01007-6

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  • DOI: https://doi.org/10.1007/s13258-020-01007-6

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