Scholar - SciOpen

To draw the genome-wide distribution and remodeling characteristics of H3K27me3 silencers in signet-ring cell carcinoma of the stomach (SRCC) through epigenetic sequencing technology, and to investigate their roles in transcriptional regulation in order to elucidate the regulatory mechanism of SRCC malignant progression.

Methods

The study was conducted on 35 gastric samples obtained by gastroendoscopic biopsy (15 normal and 20 SRCC tissues) from Department of Gastroenterology of Army Medical Center of PLA between January 2021 and December 2023. Multi-omics analyses, including assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), cleavage under targets and tagmentation (CUT&Tag) and transcriptome sequencing (RNA-seq), were performed to identify chromatin accessibility, H3K27me3 silencer regions, and transcriptional changes, with aid of Illumina NovaSeq 6000. H3K27me3 related differentially expressed genes (|Log₂FC| >1, FDR<0.05) were screened using DESeq2. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enrichment function, and Homer was employed to identify transcription factor motifs. A regulatory network was constructed using Cytoscape, and then validated using immunohistochemistry to explore its regulatory mechanism.

Results

H3K27me3 silencers were primarily located in distal intergenic regions (37.06%) in SRCC. Compared with the normal tissues, SRCC showed a significant reduction in H3K27me3 silencer signals (95%CI: 1.34~2.30, P=0.007) with 6257 lost sites (FDR<0.01). Integrating CUT&Tag and RNA-seq revealed 380 up-regulated immune-related genes, particularly in T cell receptor signaling (OR=4.2, 95%CI: 2.8~6.3, P=0.002). Immunohistochemistry confirmed elevated expression of transcription factor EHF (P<0.05).

Conclusion

There is the remodeling of H3K27me3 silencers in SRCC, and EHF may potentially play a crucial role in the SRCC malignant progression.

Open Access Review Article Issue

Roles of efferocytosis in wound repair: Process, cells, and signals

Yilin Sun, Haiying Guo, Yang Bai, Jin Chen, Yuhong Li

Genes & Diseases 2026, 13(3)

Published: 13 November 2025

Abstract

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Efficient clearance of apoptotic cells, termed efferocytosis, is essential for resolving excessive inflammation, promoting wound repair, and maintaining homeostasis. Defective clearance results in the accumulation of dead cells and other metabolites, which are responsible for chronic inflammation, nonhealing of wounds, and tissue regeneration. Emerging evidence shows that the failure to resolve inflammation and defective phagocytosis or efferocytosis increases the possibility of several diseases involving diabetic wounds and damage to the gastrointestinal mucosa in patients with inflammatory bowel disease, which is a focus of medical development and the public eye. Thus, gaining deeper insight into the molecular and cellular mechanisms of efferocytosis may be useful for inflammation resolution. This review describes the mechanism of efferocytosis and wound repair and the roles of professionals (macrophages and dendritic cells) and amateur phagocytes (e.g., epithelial cells, endothelial cells, and fibroblasts) in both processes, which may provide insight into how efferocytosis affects wound repair. Because there may be many inflammatory cells recruited to the injury area, the aim of efferocytosis is to clear these cells and release proinflammatory and anti-inflammatory mediators to promote repair. Here, we review the effects of cell-mediated efferocytosis on the timely efferocytosis of neutrophils and M1 macrophages and the relationship between M2 polarization and efferocytosis. In addition, the molecular mechanisms involved are discussed, which may further our understanding of the effects of efferocytosis. Finally, these signals also provide potential targets for tissue repair intervention.

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