Haihong Deng,1,* Qisen Fan,2,* Lichao Huang,1 Wenbo Ouyang,1 Wendian Zhu3 

1Department of Anesthesiology, The First People’s Hospital of Zhaoqing, Zhaoqing City, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First People’s Hospital of Zhaoqing, Zhaoqing City, Guangdong Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wendian Zhu, Department of Hepatobiliary Surgery, The First People’s Hospital of Zhaoqing, NO. 9 Donggang East Road, Duanzhou District, Zhaoqing City, Guangdong Province, People’s Republic of China, Email Zq2860676@163.com

Background: Myocardial ischemia/reperfusion (I/R) injury significantly impacts the recovery of ischemic heart disease patients. Non-coding RNAs, including miRNAs, have been increasingly recognized for their roles in regulating cardiomyocyte responses to hypoxia/reoxygenation (H/R) injury. miR-181c-5p, in particular, has been implicated in inflammatory and apoptotic processes, suggesting its potential involvement in exacerbating cellular damage.
Methods: This study combined bioinformatic and experimental techniques to investigate myocardial injury. Gene expression data from the GEO database were analyzed, and HL-1 cardiomyocytes were used in a hypoxia/reoxygenation model to mimic reperfusion injury. Various molecular techniques have been applied to explore the underlying mechanisms, while statistical analyses have identified potential biomarkers and therapeutic targets.
Results: This study revealed significant upregulation of miR-181c-5p in cardiomyocyte H/R injury models, which inversely affected PTPN4 expression and activated the TLR4/NF-κB signaling pathway. Overexpression of PTPN4 inhibited this pathway. Notably, circ_0001084 was identified as absorbing miR-181c-5p, reducing its interaction with PTPN4 and subsequent pathway activation. This suggests a novel therapeutic pathway for myocardial I/R injury treatment, highlighting the interplay between non-coding RNAs and cellular stress responses.
Conclusion: circ_0001084 acts as a competing endogenous RNA for miR-181c-5p, enhancing PTPN4 expression and inhibiting the TLR4/NF-κB signaling pathway. These findings offer insights into the molecular mechanisms of myocardial I/R injury and potential therapeutic targets in ischemic heart disease.

Keywords: Myocardial, Circ_0001084/miR-181c-5p/PTPN4 axis, Cardiomyocyte hypoxia, Reoxygenation, TLR4/NF-κB pathway