ELF5-Regulated lncRNA-TTN-AS1 Alleviates Myocardial Cell Injury via Recruiting PCBP2 to Increase CDK6 Stability in Myocardial Infarction

Abstract

Myocardial infarction (MI) seriously threatens the health of elderly people, and reducing myocardial injury is of great significance for the treatment of MI. LncRNA-TTN-AS1 shows protective effects on cardiomyocyte injury, while the role of TTN-AS1 in MI remains unknown. CCK8, flow cytometry, and JC-1 staining assessed cell viability, apoptosis and mitochondrial membrane potential (MMP), respectively. Cellular reactive oxygen species (ROS) and secreted lactate dehydrogenase (LDH) levels were measured. The interactions between ELF5, TTN-AS1, PCBP2 and CDK6 were explored using ChIP, luciferase reporter assay, RIP, and pull-down. The severity of MI in mice was evaluated using TTC, H&E, and TUNEL staining. The data revealed that OGD/R significantly induced ROS, mitochondrial injury and apoptosis in AC16 cells, while overexpression of ELF5 or TTN-AS1 reversed these phenomena. ELF5 transcriptionally activated TTN-AS1 through binding with its promoter. TTN-AS1 increased CDK6 stability via recruiting PCBP2. CDK6 knockdown abolished the inhibitory effects of TTN-AS1 overexpression on OGD/R-induced myocardial injury. Furthermore, overexpression of TTN-AS1 or ELF5 alleviated MI progression in mice by upregulating CDK6. Collectively, TTN-AS1 transcriptionally regulated by ELF5 alleviated myocardial apoptosis and injury during MI via recruiting PCBP2 to increase CDK6 stability, which shed new lights on exploring new strategies against MI.

Keywords:

• Myocardial infarction
• lncRNA-TTN-AS1
• transcription factor ELF5
• CDK6 signaling

Availability of data and materials

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Disclosure statement

These authors declared no competing interests in this work.

Ethics approval and consent to participate

Ethics Committee of Binhai County People’s Hospital approved this work.

Authors’ contributions

Guarantor of integrity of the entire study: Aijun Liu

Study concepts: Yonglin Zhang, Zhenglu Shang

Study design: Yonglin Zhang, Zhenglu Shang

Definition of intellectual content: Yonglin Zhang, Zhenglu Shang

Literature research: Yonglin Zhang, Zhenglu Shang, Shucan Xu

Experimental studies: Shucan Xu, Guangzhi Zhou

Data acquisition: Shucan Xu, Guangzhi Zhou

Data analysis: Shucan Xu, Guangzhi Zhou

Statistical analysis: Shucan Xu, Guangzhi Zhou

Manuscript preparation: Zhenglu Shang, Yonglin Zhang

Manuscript editing: Yonglin Zhang, Zhenglu Shang

Manuscript review: Yonglin Zhang, Aijun Liu, Zhenglu Shang

Additional information

Funding

This work was supported by Medical Research Project of Jiangsu National Health Commission, Z2021006 for YongLin Zhang.