LncRNA AC125982.2 regulates apoptosis of cardiomyocytes through mir-450b-3p/ATG4B axis in a rat model with myocardial infarction

Zhi-Jun Xu; Peng-Yin Zhang; Zhen-Qiu Li; Han-Ping Zhu; Wei-Lu Tan; Pei-Hua Ren

doi:10.1016/j.heliyon.2023.e22467

LncRNA AC125982.2 regulates apoptosis of cardiomyocytes through mir-450b-3p/ATG4B axis in a rat model with myocardial infarction

Heliyon. 2023 Nov 17;9(11):e22467. doi: 10.1016/j.heliyon.2023.e22467. eCollection 2023 Nov.

Authors

Zhi-Jun Xu¹, Peng-Yin Zhang¹, Zhen-Qiu Li², Han-Ping Zhu², Wei-Lu Tan², Pei-Hua Ren²

Affiliations

¹ Guangzhou Medical University, Guangzhou, 511436, China.
² Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Abstract

Background: The occurrence and disability of myocardial infarction (MI) are on the rise globally, making it a significant contributor to cardiovascular mortality. Irreversible myocardial apoptosis plays a crucial role in causing MI. Long non-coding RNAs (LncRNAs) are key regulators of the cardiac remodeling process. Therefore, it is necessary to explore the effect of LncRNAs on cardiomyocyte apoptosis in MI.

Methods: The rat-MI model was constructed, LncRNA-Seq and qPCR analyses were used to determine differentially expressed genes obtained from heart tissue of rats in the MI and sham groups. The miRanda software was used to predict the binding sites of LncRNA-miRNA and miRNA-mRNA, which were futhrer verified by dual luciferase assay. The LncRNA-miRNA-apoptosis pathway was further validated using hypoxia-exposed primary cardiomyocytes.

Results: Compared to the sham group, 412 LncRNAs were upregulated and 501 LncRNAs were downregulated in MI-rat heart tissues. Among them, LncRNA AC125982.2 was most significantly upregulated in MI-rat heart tissues and hypoxic cardiomyocytes. Knockdown of AC125982.2 and ATG4B expression reversed hypoxia-induced apoptosis. In addition, transfection of mir-450b-3p inhibitor attenuated the protective effect of AC125982.2 knockdown. Moreover, we found that AC125982.2 modulated ATG4B expression by acting as a sponge for miR-450b-3p.

Conclusion: Upregulated AC125982.2 expression regulates ATG4B by sponging miR-450b-3p, promoting cardiomyocyte apoptosis and contributing to rat MI development.

Keywords: ATG4B; LncRNA AC125982.2; Mir-450b-3p; Myocardial infarction; ceRNA.