ca-circSCN8A Promotes HPASMCs Ferroptosis via LLPS Initiated R-Loop
ca-circSCN8A recruits EP300 to promote the lactylation of FUS, thereby driving liquid-liquid phase separation-mediated complex formation with FUS and EP300. This process enables ca-circSCN8A to form an R-loop with the nonhost SLC7A11 promoter, contributing to the regulation of hypoxia-induced ferroptosis in human pulmonary arterial smooth muscle cells. This study provides the first evidence that circRNAs can form R-loops with nonhost genes in a liquid-liquid phase separation-dependent manner. Our findings highlight ca-circSCN8A as a crucial regulator of ferroptosis in hypoxic PH and a potential therapeutic target for PH.
Authors
- Xiaodong Zheng (ORCID: https://orcid.org/0000-0002-6103-9836)
- Hanliang Sun
- Cui Ma (ORCID: https://orcid.org/0000-0001-8413-5284)
- Daling Zhu (ORCID: https://orcid.org/0000-0002-6669-2236)
- Chi Zhang (ORCID: https://orcid.org/0009-0004-6555-5389)
- Yingying Hao (ORCID: https://orcid.org/0000-0001-7682-4063)
- Xinyue Song (ORCID: https://orcid.org/0000-0001-8238-309X)
- Jiaqi Zhang (ORCID: https://orcid.org/0000-0002-3143-5651)
- Hang Yu (ORCID: https://orcid.org/0000-0001-7927-0473)
- Xijuan Zhao (ORCID: https://orcid.org/0000-0002-9253-9200)
- Mengnan Li (ORCID: https://orcid.org/0000-0001-7461-3254)
- Lixin Zhang (ORCID: https://orcid.org/0000-0002-6177-4152)
- Huiyu Liu (ORCID: https://orcid.org/0000-0003-4465-8501)
Institutions
- Harbin Medical University (CN)
Publication Details
- Journal
- Hypertension
- Published
- 2025-05-19
- DOI
- https://doi.org/10.1161/hypertensionaha.125.25036
- Citations
- 7
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 5.64