ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Clinical and Translational Cardiovascular Medicine
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1639767
Expression Profiles and Bioinformatic Analysis of Circular RNA in Rheumatic Heart Disease: Potential hsa_circ_0001490 and hsa_circ_0001296 as a Diagnostic Biomarker
Provisionally accepted
- Ningbo Medical Centre Lihuili Hospital, Ningbo, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: This study aimed to investigate the expression profiles of circRNAs and construct a circRNA-miRNA-mRNA interaction network to reveal new diagnostic biomarkers and potential pathogenesis of RHD. Methods: Clinical data and plasma samples from 46 patients with RHD and 46 non-RHD patients were collected between January 2021 and December 2023. Arraystar Human CircRNA microarray was used to profile differentially expressed circRNAs in 3 paired samples (RHD vs. non-RHD). Quantitative real-time PCR validated four candidate circRNAs in all 92 samples. The diagnostic value of differentially expressed circRNAs was analyzed by the Receiver Operating Characteristic(ROC) Curve. Bioinformatics analysis was used to predict the target miRNA and analyze the co‑expressed mRNA to construct a circRNA–miRNA-mRNA regulatory network. The (GO) and KEGG pathway enrichment analyses were conducted to predict the potential functions of the differentially expressed genes and RHD-related pathways. Results: Four circRNAs were selected from circRNA microarray data. qRT-PCR confirmed that hsa_circ_0001490 and hsa_circ_0001296 were significantly upregulated in RHD plasma (4.28-fold, P < 0.001; 5.24-fold, P < 0.001, respectively). ROC analysis revealed hsa_circ_0001490 had an AUC of 0.792 (95% CI: 0.69–0.89; sensitivity: 93.5%; specificity: 67.4%), while hsa_circ_0001296 showed superior accuracy (AUC = 0.896; 95% CI: 0.83–0.96; sensitivity: 69.6%; specificity: 95.7%). A predicted hsa_circ_0001490‑miRNA‑mRNA regulatory network included 11 miRNAs and 1,973 mRNAs, and hsa_the circ_0001296‑miRNA‑mRNA interaction network included 9 miRNAs and 1,404 mRNAs. Moreover, the top 10 hub genes were screened within the two networks, respectively. Functional enrichment analysis revealed that downstream genes of hsa_circ_0001490 were significantly associated with Smad binding and regulation of the Wnt signaling pathway (GO terms), as well as the Wnt and TGF-β signaling pathways (KEGG pathways). For hsa_circ_0001296, we identified significant enrichment for transforming growth factor beta receptor type I activity and Smad binding (GO terms), along with the autophagy and MAPK signaling pathways (KEGG pathways). Conclusion: This study provides the first evidence of significant upregulation of hsa_circ_0001490 and hsa_circ_0001296 in RHD patients, suggesting their potential as diagnostic biomarkers for RHD. The constructed circRNA-miRNA-mRNA network reveals potential molecular mechanisms underlying RHD pathogenesis. Future studies should investigate these circRNAs' functional roles to fully elucidate their contribution to RHD development.
Keywords: circular RNA, Rheumatic heart diseases, regulatory network, diagnosis, biomarker
Received: 02 Jun 2025; Accepted: 22 Jul 2025.
Copyright: © 2025 Xiaoliang, Lina, Li, Shunying, Xiaoyan, Ni, Linwen and Guofeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shao Guofeng, Ningbo Medical Centre Lihuili Hospital, Ningbo, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.