Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

Ke Gong; Kai Yang; Ting Xie; Yong Luo; Hui Guo; Zhiping Tan; Jinlan Chen; Qin Wu; Yibo Gong; Luyao Wei; Jinwen Luo; Yao Yao; Yifeng Yang; Li Xie

doi:10.1371/journal.pone.0279638

Identification of circRNA-miRNA-mRNA regulatory network and its role in cardiac hypertrophy

PLoS One. 2023 Mar 23;18(3):e0279638. doi: 10.1371/journal.pone.0279638. eCollection 2023.

Authors

Ke Gong¹, Kai Yang², Ting Xie¹, Yong Luo¹, Hui Guo¹, Zhiping Tan^{1

3}, Jinlan Chen¹, Qin Wu¹, Yibo Gong¹, Luyao Wei¹, Jinwen Luo⁴, Yao Yao⁵, Yifeng Yang¹, Li Xie¹

Affiliations

¹ Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, P.R. China.
² Department of Plastic Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, P.R. China.
³ The Clinical Center for Gene Diagnosis and Therapy of The State Key Laboratory of Medical Genetics, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, P.R. China.
⁴ Department of Cardiothoracic Surgery, Hunan Children's Hospital, Changsha, Hunan, P.R. China.
⁵ Department of Blood Transfusion, The Second Xiangya Hospital of Central South University, Central South University, Changsha, P.R. China.

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is a grave hazard to human health. Circular RNA (circRNAs) and micro RNA (miRNAs), which are competitive endogenous RNA, have been shown to play a critical role inHCM pathogenicity. However, to a great extent, the biological activities of ceRNA in HCM pathophysiology and prognosis remain to be investigated.

Materials and methods: By analyzing the expression files in the Gene Expression Comprehensive (GEO) database, differentially expressed (DE) circRNAs, miRNAs, and mRNAs in HCM were identified, and the target molecules of circRNAs and miRNAs were predicted. The intersection of the differentially expressed RNA molecules and the expected target was then calculated, and a ceRNA network was subsequently constructed using RNA molecules. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the potential etiology was elucidated. qPCR was used to validate a portion of the hub gene using Angiotensin II to generate a cell hypertrophy model.

Results: Three large-scale HCM sample datasets were extracted from the GEO database. After crossing these molecules with their expected targets, the circRNA-miRNA-mRNA network had two DEcircRNAs, two DEmiRNAs, and thirty DEmRNAs, compared to normal tissues. Functional enrichment analysis of GO and KEGG demonstrated that many of the HCM pathways and mechanisms were associated with calcium channel release, which is also the primary focus of future research. The qPCR results revealed that circRNA, miRNA, and mRNA expression levels were different. They may include novel noninvasive indicators for the early screening and prognostic prediction of HCM.

Conclusion: In this study, we hypothesized a circRNA-miRNA-mRNA regulation network that is closely related to the progression and clinical outcomes of HCM and may contain promising biomarkers and treatment targets for HCM.

Copyright: © 2023 Gong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cardiomegaly / genetics
Cardiomyopathy, Hypertrophic* / genetics
Gene Regulatory Networks
Humans
MicroRNAs* / genetics
RNA, Circular / genetics
RNA, Messenger / genetics

Substances

RNA, Circular
MicroRNAs
RNA, Messenger

Grants and funding

This study was supported by the National Natural Science Foundation of China (81500245), National Natural Science Foundation of Hunan(2016JJ4099, 2019JJ50858 and 2022JJ30856), Scientific Research Plan of the Hunan Provincial Health Commission(202204022475), the Central Universities of Central South University (2022ZZTS0951) and Hunan Provincial Natural Science Foundation of China (2016JJ4099). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.