Full
Outline
To explore the impact of epigenetic remodeling-mediated regulation of circadian genes on ferroptosis in gastric cancer cells.
The data from Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), bulk RNA sequencing (RNA-seq), and single-cell RNA sequencing (scRNA-seq) were integrated to identify candidate transcription factors recruited by open chromatin regions in gastric cancer. Then, NPAS2, a circadian rhythm-related transcription factor, was identified as a key regulator. Immunohistochemical assay and survival analysis were performed to investigate the relationship of NPAS2 overexpression with tumor progression and poor prognosis. Bioinformatics analysis was conducted to analyze the correlation between NPAS2 and the ferroptosis pathway. Functional experiments were carried out through NPAS2 knockdown and overexpression in gastric cancer cell lines. Cell viability (CCK-8), malondialdehyde (MDA) measurement, BODIPY fluorescence staining, and flow cytometry were employed to confirm the role of NPAS2 in inhibiting ferroptosis in gastric cancer cells.
NPAS2 was significantly highly expressed at both mRNA and protein levels during gastric cancer progression, and its high expression was strongly correlated with poor prognosis. Its high expression was associated with inactivation of ferroptosis pathway, and ferroptosis-suppressive genes such as SLC7A11 and ACSL3 were markedly up-regulated in NPAS2-high gastric cancer tissues. In vitro, NPAS2 overexpression enhanced ferroptosis resistance, whereas NPAS2 knockdown significantly promoted ferroptosis in gastric cancer cells.
Open chromatin in gastric cancer can upregulate the rhythm factor NPAS2, which promotes tumor progression by conferring ferroptosis resistance to gastric cancer cells and serves as a potential therapeutic target.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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