Aim
Long non-coding RNA SOX2 overlapping transcript (SOX2OT) is closely related to heart failure and myocardial damage. We attempted to investigate its role in endotoxin lipopolysaccharide (LPS) injury in cardiomyocytes. Materials &
Conclusion
Inhibiting SOX2OT/miR-215-5p/ICAM1 axis might be a possible approach to treat myocardial damage. Lay abstract: Lipopolysaccharide (LPS) is an endotoxin from some bacteria including Escherichia coli, and it can cause inflammation in different tissues/cells including myocardia/cardiomyocytes, resulting in diseases such as myocarditis, cardiomyopathy, and cardiac hypertrophy. The underlying mechanism was not completely clarified, but known to include the dysregulation of non-coding RNAs. Herein, we demonstrated the biological role of long non-coding RNA SOX2 overlapping transcript (SOX2OT) in LPS-infected cardiomyocytes. Eventually, we found that inhibiting the expression of SOX2OT could mitigate LPS-induced a series of injuries in human cardiomyocytes, and SOX2OT interacts with a microRNA named as miR-215-5p. Besides, restoring miR-215-5p elicited similar effects to SOX2OT knockdown. Collectively, we concluded that SOX2OT binding to miR-215-5p might protect cardiomyocytes from LPS infection through regulating an important protein named ICAM1. This study suggested SOX2OT/miR-215-5p might be novel potential treatment targets in bacterial infection-related myocardial damages.
Methods
Cell viability, apoptosis rate, and levels of pro-inflammatory cytokines and apoptosis- and oxidative stress-related proteins were measured by MTS assay kit, flow cytometry, western blotting, and commercial kits. Physical interactions were confirmed by dual-luciferase report assay and RNA immunoprecipitation assay.
Results
Silencing SOX2OT and reinforcing miRNA (miR)-215-5p protected human AC16 cardiomyocytes from LPS-induced oxidative and inflammatory injuries by inhibiting intercellular adhesion molecule 1 (ICAM1). SOX2OT directly interacted with miR-215-5p, and miR-215-5p could target ICAM1.