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.
Acknowledgments
We thank Taylor & Francis Editing Services Team (www.tandfeditingservices.com) and AiMi Academic Services (www.aimieditor.com) for the English language editing and review services.
Authors’ contributions
Bimei Jiang conceived and designed the project. Cheng Chen and Xiaofang Lin conducted the majority of the experiments and analyzed the data. Yuting Tang, Hui Sun, Leijing Yin, Zhengyang Luo, and Shuxin Wang performed some experiments. Cheng Chen and Xiaofang Lin wrote this manuscript. Cheng Chen and Xiaofang Lin are the co-first authors. All authors have read and approved the final manuscript.
Data availability statement
The data used and analyzed during the current study are available from the corresponding author upon reasonable request.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Ethical approval
This study was approved by the Clinical Ethics Committee of the Central South University.