Evidence map›Paper›PMID 40530493›Full record

ArticleJournal of the American Heart Association2025

Circ-myh8/KAT7 Affects PANoptosis in Pulmonary Arterial Smooth Muscle Cells: Involvement of Super-Enhancers in FOSL2 Expression.

Jingya Zhang, Xinru Wang, Xu Wang, Songyue Li, Jianli Hou, Yibin Zhang, Xinyue Song, Shukun Cao, Ya Xu, Jing Qi and 3 more

Abstract read
In one paragraph

Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Jingya ZhangDepartment of Pharmacology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.
Xinru WangDepartment of Pharmacology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.ORCID 0009-0001-4446-4961
Xu WangDepartment of Pharmacology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.
Songyue LiDepartment of Pharmacology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.ORCID 0000-0001-7161-3881
Jianli HouDepartment of Pharmacology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.
Yibin ZhangDepartment of Pharmacology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.
Xinyue SongCollege of Pharmacy Harbin Medical University Harbin Heilongjiang People's Republic of China.
Shukun CaoDepartment of Medical Genetics Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.
Ya XuCollege of Pharmacy Harbin Medical University Harbin Heilongjiang People's Republic of China.ORCID 0009-0003-6668-9373
Jing QiDepartment of Pharmacology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.
Baoshan ZhaoDepartment of Pathology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.ORCID 0000-0003-1583-3083
Xiaodong ZhengDepartment of Medical Genetics Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.ORCID 0000-0002-6103-9836
Yan XingDepartment of Pharmacology Harbin Medical University-Daqing Daqing Heilongjiang People's Republic of China.ORCID 0009-0006-0322-3228

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPulmonary hypertension is a pathophysiological condition characterized by multiple forms of regulated cell death. PANoptosis, which is an inflammation-driven mode of regulated cell death, is regulated by the PANoptosome. Super-enhancers (SEs) have been implicated in the pathology of pulmonary hypertension by modulating the transcriptional regulation of target genes. However, it remains unclear whether SEs influence the onset of PANoptosis in pulmonary arterial smooth muscle cells (PASMCs) via the regulation of specific target genes.

methodsChromatin immunoprecipitation (ChIP)-sequencing was integrated with RNA sequencing to identify SE-regulated target genes in hypoxic PASMCs. Bioinformatics analysis was used to predict transcription factors with potential binding sites in the promoter or SE regions of these target genes. Coimmunoprecipitation and ChIP-polymerase chain reaction were conducted to validate the epigenetic regulatory mechanisms governing SE-regulated target genes. Immunoblotting was performed to assess the expression of PANoptosis proteins, whereas YP1 (YO-PRO-1; Oxazole yellow) and PI (propidium iodide) fluorescence staining and immunofluorescence were used to evaluate the effects of transcription factors and SE on PANoptosis in PASMCs. Additionally, reverse transcriptase-quantitative polymerase chain reaction, immunoblotting, and ChIP-polymerase chain reaction assays were used to investigate the impact of the SE region of the target gene on PANoptosis in PASMCs following CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9)-mediated knockdown of the SE regions of the target genes.

resultsA combination of ChIP sequencing and RNA sequencing analyses confirmed that

conclusionsCirc-myh8 RNA, which functions jointly with KAT7, enhances H3K27ac enrichment, thereby promoting SE activity for FOSL2 transcription. This process ultimately contributes to the induction of PANoptosis in PASMCs. These findings elucidate the role of the circ-myh8/KAT7/SE/FOSL2 axis in the regulation of PANoptosis in PASMCs, thus offering new insights into the pathophysiology of PANoptosis in pulmonary hypertension. These findings may lead to novel therapeutic strategies for the treatment of pulmonary hypertension.

Indexed as

Enhancer Elements, GeneticFos-Related Antigen-2Muscle, Smooth, VascularMyocytes, Smooth MusclePulmonary ArteryRNA, CircularAnimalsCells, CulturedEpigenesis, GeneticGene Expression RegulationHumansMaleRatsFOSL2 protein, humanFos-Related Antigen-2RNA, CircularFOSL2PANoptosispulmonary hypertensionsuper‐enhancer

Identifiers

PMID40530493
PMCPMC12449935

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.