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ORIGINAL RESEARCH article

Front. Genet.

Sec. RNA

This article is part of the Research TopicComplex Interplay Between Lung Diseases and Multisystem Disorders: Pathogenesis, management, and OutcomeView all 14 articles

Sex-specific circRNA-miRNA-mRNA Networks in Peripheral Blood Mononuclear Cells of Patients with Idiopathic Pulmonary Arterial Hypertension: a Pilot Study

Provisionally accepted
  • 1Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China
  • 2The Second Xiangya Hospital of Central South University, Changsha, China
  • 3Shandong Provincial Hospital, Jinan, China

The final, formatted version of the article will be published soon.

Background Idiopathic pulmonary artery hypertension (IPAH) is a life-threatening condition with obvious sex differences. Recently, the interactions among circRNAs, miRNAs and mRNAs were found as significant parts in IPAH. Thus, we want to explore whether there exist RNA networks in IPAH via sex differential analyses. Methods and Materials Illumina Hiseq was used to detect differential expressed (DE) RNAs in peripheral blood mononuclear cells (PBMCs) from 6 (3 males) IPAH patients. GO and KEGG pathway analyses were employed for exhibition of differential expression levels of circRNAs, miRNAs and mRNAs. The competing endogenous RNA (ceRNA) networks among circRNAs, miRNAs and mRNAs were constructed on the basis of the authoritative miRanda and TargetScan databases. Student's t test was employed and P<0.05 was applied to show significance. Results There were 220 DE circRNAs (106 upregulation and 104 downregulation), 41 DE miRNAs (15 upregulation and 26 downregulation), and 160 mRNAs (65 upregulation and 95 downregulation) in the female group compared with the male group, respectively. Through interactions analyses among circRNAs, miRNAs and mRNAs, upregulated has-miR-1304-3p might were sponged to hsa-circ-0005723 and hsa-circ-0030276 and downregulated hsa-miR-6859-3p was probably sponged to circ DGKD, to modulate 21 downregulation genes and 6 upregulation genes, respectively. Conclusion There were sex differences of a comprehensive circRNA–miRNA– mRNA regulatory network in IPAH.

Keywords: IPAH, sex difference, circRNA, miRNA, Molecular signature

Received: 30 Jul 2025; Accepted: 06 Nov 2025.

Copyright: © 2025 Yuan, Sun, Huang, Hu and Yuan. 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: Ping Yuan, pandyyuan@tongji.edu.cn

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