Tcf3‐activated lncRNA Gas5 regulates newborn mouse cardiomyocyte apoptosis in diabetic cardiomyopathy

• Published in: Journal of cellular biochemistry Vol. 121; no. 11; pp. 4337 - 4346
• Main Authors: Su, Dongsheng, Ju, Yansong, Han, Wei, Yang, Yanhua, Wang, Fengyun, Wang, Tong, Tang, Jianmin
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2020
• Subjects: Apoptosis; Assaying; Cardiomyocytes; Cardiomyopathy; Congestive heart failure; Diabetes; Diabetes mellitus; diabetic cardiomyopathy; DNA nucleotidylexotransferase; Flow cytometry; Gas5; miR‐320‐3p; Ribonucleic acid; RNA; Tcf3; Tcf3; diabetic cardiomyopathy; Gas5; miR-320-3p
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.29630

Diabetic cardiomyopathy can cause cardiac dysfunction and eventually lead to heart failure and sudden death. Long noncoding RNA (lncRNA) Gas5 has been reported to play a function in cardiomyocyte. Here we studied the function of Gas5 on newborn mouse cardiomyocyte (NMC) apoptosis to detect its molecular mechanism. High‐glucose treatment was implemented to induce the apoptosis of NMC in this study. And terminal deoxynucleotidyl transferase dUTP nick‐end labeling assay, JC‐1 assay, and flow cytometry analysis were conducted to know about the apoptosis of NMC when Gas5 and Tcf3 were silenced. Meanwhile, RNA pull‐down assay and luciferase reporter assay were conducted to verify the binding of RNAs. Finally, rescue assay was implemented to evaluate the influence on apoptosis situation affected by competing endogenous RNA pathways. Tcf3 was found to bind to the Gas5 promoter to activate the expression of Gas5. Meanwhile, Gas5 and Tcf3 were both found to promote the apoptosis of NMC. Also, mmu‐miR‐320‐3p could bind to Gas5 and Tcf3. Moreover, the Gas5/miR‐320‐3p/Tcf3 pathway was found to modulate the apoptosis of NMC. In conclusion, Tcf3‐activated lncRNA Gas5 regulates NMC apoptosis in diabetic cardiomyopathy. Inhibited Gas5 and Tcf3 could reduce the apoptosis of newborn rat cardiomyocyte (NRC) and newborn mouse cardiomyocyte (NMC). miR‐320‐3p could bind to Tcf3 and Gas5 in NRC and NMC.