# Hsa_circ_0005623 is an indicator for pulmonary artery hypertension associated with congenital heart disease

**Authors:** Yuanhao Zhang, Yan Han, Zirui Sun, Weizhen Xing, Hao Tang, Chuanyu Gao, Yu Han

PMC · DOI: 10.3389/fcvm.2025.1561069 · Frontiers in Cardiovascular Medicine · 2026-01-12

## TL;DR

The study identifies hsa_circ_0005623 as a potential early biomarker for pulmonary artery hypertension linked to congenital heart disease.

## Contribution

hsa_circ_0005623 is newly identified as a plasma biomarker for early diagnosis of PAH.

## Key findings

- hsa_circ_0005623 is significantly downregulated in PAH patients.
- Low hsa_circ_0005623 levels correlate with increased mean pulmonary artery pressure.
- A ceRNA network involving hsa_circ_0005623 is linked to endothelium development and blood vessel migration.

## Abstract

There is a strong correlation between delayed diagnosis and high mortality rate in pulmonary arterial hypertension (PAH). Recent research indicates that circular RNAs (circRNAs) may serve as potential diagnostic biomarkers for PAH. This study aimed to identify important circRNAs associated with PAH to support early diagnosis and explore possible key disease mechanisms. GSE171827 and GSE113439 were obtained from the Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (DECs) and genes (DEGs). MicroRNAs (miRNAs) related to PAH were obtained from the Human microRNA Disease Database (HMDD). We validated changes in DEC expression levels using RT-qPCR in hypoxia- and normoxic-induced human pulmonary artery endothelial cells. Then, the potential relationship between DEC expression levels and mean pulmonary artery pressure (mPAP) in PAH patients was investigated. Finally, bioinformatics analyses were performed to construct a competing endogenous RNA (ceRNA) network and excavate the potential functions of DECs. Only hsa_circ_0005623 expression was significantly downregulated in PAH. Low hsa_circ_0005623 expression levels in the plasma of PAH patients were significantly associated with mPAP (p < 0.001). A ceRNA network comprising 1 circRNA (hsa_circ_0005623), 4 miRNAs (has-miR-424-5p, has-miR-503-5p, has-miR-331-3p, and has-miR-17-3p), and 10 mRNAs (CDH5, ANGPT2, DLL4, CLDN5, ANGPTL4, EDN1, HEY1, GATA2, CLEC14A, and ADM) was identified. Functional enrichment analysis of these 10 hub genes showed enrichment in endothelium development and blood vessel endothelial cell migration. These results suggest that hsa_circ_005623 in plasma is a potential biomarker for early PAH and may play an important role in the development of PAH.

## Linked entities

- **Genes:** CDH5 (cadherin 5) [NCBI Gene 1003], ANGPT2 (angiopoietin 2) [NCBI Gene 285], DLL4 (delta like canonical Notch ligand 4) [NCBI Gene 54567], CLDN5 (claudin 5) [NCBI Gene 7122], ANGPTL4 (angiopoietin like 4) [NCBI Gene 51129], EDN1 (endothelin 1) [NCBI Gene 1906], HEY1 (hes related family bHLH transcription factor with YRPW motif 1) [NCBI Gene 23462], GATA2 (GATA binding protein 2) [NCBI Gene 2624], CLEC14A (C-type lectin domain containing 14A) [NCBI Gene 161198], ADM (adrenomedullin) [NCBI Gene 133]
- **Diseases:** pulmonary arterial hypertension (MONDO:0015924), congenital heart disease (MONDO:0005453)

## Full-text entities

- **Genes:** HAS1 (hyaluronan synthase 1) [NCBI Gene 3036] {aka HAS}, MIR17 (microRNA 17) [NCBI Gene 406952] {aka MIR17-5p, MIR91, MIRN17, MIRN91, hsa-mir-17, miR-17}, GATA2 (GATA binding protein 2) [NCBI Gene 2624] {aka DCML, IMD21, MONOMAC, NFE1B}, HEY1 (hes related family bHLH transcription factor with YRPW motif 1) [NCBI Gene 23462] {aka BHLHb31, CHF2, HERP2, HESR1, HRT-1, NERP2}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, ANGPTL4 (angiopoietin like 4) [NCBI Gene 51129] {aka ARP4, FIAF, HARP, HFARP, NL2, PGAR}, CLEC14A (C-type lectin domain containing 14A) [NCBI Gene 161198] {aka C14orf27, CEG1, EGFR-5}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, DLL4 (delta like canonical Notch ligand 4) [NCBI Gene 54567] {aka AOS6, delta4, hdelta2}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, CDH5 (cadherin 5) [NCBI Gene 1003] {aka 7B4, CD144}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}, ADM (adrenomedullin) [NCBI Gene 133] {aka AM, PAMP}
- **Diseases:** hypoxia (MESH:D000860), PAH (MESH:D000081029), congenital heart disease (MESH:D006330)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12833378/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12833378/full.md

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Source: https://tomesphere.com/paper/PMC12833378