Int. J. Dev. Biol. 67: 9 - 17 (2023)

https://doi.org/10.1387/ijdb.220150jl

Vol 67, Issue 1

Circ-JA760602 promotes the apoptosis of hypoxia-induced cardiomyocytes by transcriptionally suppressing BCL2

Original Article | Published: 5 April 2023

Chao Li¹, Jingwen Wang², Jun Feng³, Gaoliang Zhou³, Yongjin Jiang³, Chunmiao Luo³, Ziping Cheng⁴, Jiehua Li*^,4

¹Department of Cardiology, the First Affiliated Hospital of Anhui Medical University; the Fifth Clinical College, Medical University of Anhui; Hefei Hospital Affiliated to Medical University of Anhui (the Second People’s Hospital of Hefei), Hefei, Anhui, China, ²Department of Cardiology, the Second Hospital Affiliated to Medical University of Anhui, Hefei, Anhui Province, China, ³Department of Cardiology, Hefei Hospital Affiliated to Medical University of Anhui (the Second People’s Hospital of Hefei), Hefei, Anhui Province, China, ⁴Department of Cardiology, the First Hospital Affiliated to Medical University of Anhui, Hefei, Anhui Province, China

Abstract

Acute myocardial infarction (AMI) is myocardial necrosis caused by the complete or partial obstruction of a coronary artery. Circular RNAs (circRNAs) have been proven as regulators in the progression of various human diseases, including AMI. However, the role of novel circ-JA760602 in AMI remains unknown. Here, we investigated the role of circ-JA760602 in modulating the apoptosis of hypoxia-induced AMI cells using the AC16 cardiomyocyte in vitro cell model. The expression of circ-JA760602 in AC16 cardiomyocytes subjected to hypoxia was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was measured by cell counting kit-8 (CCK-8) assay. Apoptosis of cardiomyocytes was evaluated by TUNEL assay and flow cytometry analysis. The cellular location of circ-JA760602 was identified through fluorescence in situ hybridization (FISH) assay and subcellular fractionation assay. The downstream molecular mechanisms of circ-JA760602 were demonstrated by luciferase reporter assay, RNA binding protein immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. Rescue assays were performed to demonstrate the effects of BCL2 knockdown on circ-JA760602 silencing-mediated cardiomyocyte apoptosis. Circ-JA760602 expression was elevated after hypoxia treatment. Knockdown of circ-JA760602 enhanced viability and curbed apoptosis of hypoxia-treated cardiomyocytes. EGR1 and E2F1 could activate BCL2 transcription. Cytoplasmic circ-JA760602 bound with EGR1 and E2F1 to thus inhibit their nuclear translocation. BCL2 knockdown reversed the effects of circ-JA760602 silencing on the apoptosis of hypoxia-treated AC16 cells. Circ-JA760602 promotes hypoxia-induced apoptosis of cardiomyocytes by binding with EGR1 and E2F1 to inhibit the transcriptional activation of BCL2.

Keywords

circ-JA760602, BCL2, apoptosis, acute myocardial infarction