Construction of a ceRNA network of regulated ferroptosis in doxorubicin-induced myocardial injury

Abstract

Background Ferroptosis and long-noncoding RNAs (lncRNAs) play crucial roles in doxorubicin (DOX)-induced myocardial injury (DIMI). Nevertheless, there is no research to construct competing endogenous RNAs (ceRNAs) network between lncRNAs and ferroptosis-related key gene. So our research was designed to screen ferroptosis-related genes from differentially expressed mRNAs in DIMI and construct lncRNAs regulated ferroptosis-related key gene ceRNAs network. Methods The male mice were injected with DOX intraperitoneally to induce myocardial injury, myocardial injury was evaluated by hematoxylin and eosin (HE) staining, and ferroptosis-related protein-glutathione peroxidase 4 (GPx4) protein expression was detected. The differentially expressed lncRNAs and mRNAs were detected by microarray, and the ferroptosis-related genes were screened to construct a protein-protein associations (PPA) network, the highest maximal clique centrality (MCC) score gene were identified by Cytoscape software, miRNAs bound to key genes and lncRNAs bound to miRNAs were predicted; then, the obtained lncRNAs were intersected with differentially expressed lncRNAs detected by microarray. Finally, the lncRNA/miRNA/mRNA ceRNA network of the highest MCC score gene regulating ferroptosis in DIMI was constructed. The expressions of the key components in ceRNA network were detected by qRT-PCR. Results Compared with the control group, in the DOX group, myocardial enzymes and HE staining showed that myocardium structure was changed, and GPx4 protein expression was decreased. The differentially expressed 10,265 lncRNAs and 6,610 mRNAs in the DOX group were detected via microarray. Among them, 114 ferroptosis-related genes were obtained to construct PPA networks, and Becn1 was identified as the key gene. Finally, the ceRNA network including Becn1, three miRNAs and four lncRNAs was constructed by predicting data of the Starbase database. The relative expressions of these components in ceRNA net were up-regulated and consistent with microarray results. Conclusions Based on the microarray detection results and bioinformatics analysis, we screened ferroptosis-related gene Becn1 and constructed the lncRNA/miRNA/mRNA ceRNA network of regulated ferroptosis in DIMI.

Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury

“…In recent years, much attention has been paid to studying the role of non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs in the pathogenesis of cardiovascular diseases, in particular, in the regulation of ferroptosis [60,61].…”

Identification of Ferroptosis-related Genes and Its CeRNA Network in Hypertrophic Cardiomyopathy Based on Bioinformatic Analysis

“…A growing number of evidence suggests that long non-coding RNA (lncRNA) could repress target mRNAs through miRNA response elements of a lncRNA-associated competing endogenous RNA (ceRNA) network and serve as a crucial regulatory mechanism in HCM such as cardiac hypertrophy-related factor (CHRF), ROR, H19, Plscr4, MEG3 and CYTOR [8]. Meanwhile, a large number of studies have shown that lncRNAassociated ceRNA regulatory networks also play an important role in ferroptosis [9][10][11][12], suggesting a possible regulatory role for ferroptosis-related ceRNA regulatory networks in hypertrophic cardiomyopathy.…”

Identification of Ferroptosis-related Genes and Their CeRNA Network in Hypertrophic Cardiomyopathy Based on Bioinformatic Analysis

“…A growing number of evidence suggests that long non-coding RNA (lncRNA) may repress target mRNAs through miRNA response elements of an lncRNA-associated competing endogenous RNA (ceRNA) network and serve as a critical regulatory mechanism in HCM such as cardiac hypertrophy-related factor (CHRF), ROR, H19, Plscr4, MEG3 and CYTOR [8]. Numerous studies indicate that lncRNA-associated ceRNA regulatory networks have an essential function in ferroptosis [9][10][11][12], suggesting a potential regulatory role for ferroptosis-related ceRNA regulatory networks in hypertrophic cardiomyopathy.…”