LncRNA Fendrr: involvement in the protective role of nucleolin against H2O2-induced injury in cardiomyocytes

Cheng Chen; Xiaofang Lin; Yuting Tang; Hui Sun; Leijing Yin; Zhengyang Luo; Shuxin Wang; Pengfei Liang; Bimei Jiang

doi:10.1080/13510002.2023.2168626

LncRNA Fendrr: involvement in the protective role of nucleolin against H₂O₂-induced injury in cardiomyocytes

Redox Rep. 2023 Dec;28(1):2168626. doi: 10.1080/13510002.2023.2168626.

Authors

Cheng Chen¹, Xiaofang Lin¹, Yuting Tang¹, Hui Sun¹, Leijing Yin¹, Zhengyang Luo¹, Shuxin Wang¹, Pengfei Liang², Bimei Jiang¹

Affiliations

¹ Department of Pathophysiology, Sepsis Translational Medicine Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.
² Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Abstract

Background: Nucleolin is a multifunctional nucleolar protein with RNA-binding properties. Increased nucleolin expression protects cells from H₂O₂-induced damage, but the mechanism remains unknown. Long noncoding RNAs (lncRNAs) play crucial roles in cardiovascular diseases. However, the biological functions and underlying mechanisms of lncRNAs in myocardial injury remain unclear.Methods: In a nucleolin-overexpressing cardiac cell line, high-throughput technology was used to identify lncRNAs controlled by nucleolin. Cell counting kit-8 assay was used to determine cell viability, lactate dehydrogenase (LDH) assay to detect cell death, caspase activity assay and propidium iodide staining to confirm cell apoptosis, and RNA immunoprecipitation to examine the interaction between Fendrr and nucleolin.Results: We found that Fendrr expression was significantly downregulated in mouse hearts subjected to myocardial ischemia-reperfusion (MI/R) injury. High Fendrr expression abrogated H₂O₂-mediated injury in cardiomyocytes as evidenced by increased cell viability and decreased cell apoptosis. Conversely, Fendrr knockdown exacerbated the cardiomyocytes injury. Also, nucleolin overexpression inhibits Fendrr downregulation in H₂O₂-induced cardiomyocyte injury. Fendrr overexpression significantly reversed the role of the suppression of nucleolin expression in H₂O₂-induced cardiomyocytes.Conclusion: LncRNA Fendrr is involved in the cardioprotective effect of nucleolin against H₂O₂-induced injury and may be a potential therapeutic target for oxidative stress-induced myocardial injury.

Keywords: Fendrr; Nucleolin; apoptosis; cardiomyocyte; hydrogen peroxide; injury; lncRNA; oxidative stress.

MeSH terms

Animals
Apoptosis
Hydrogen Peroxide / pharmacology
Mice
Myocardial Reperfusion Injury* / genetics
Myocardial Reperfusion Injury* / metabolism
Myocytes, Cardiac / metabolism
Nucleolin
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism

Substances

RNA, Long Noncoding
Hydrogen Peroxide

Grants and funding

This work was supported by National Natural Science Foundation of China: [grant no. 81770306, 81971820, 81974287]; the Natural Science Foundation of Hunan Province: [grant no 2018JJ2547].