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RNA-seq in parental and resistant non-small cell lung cancer (NSCLC) cells

GSE269805 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/09/16 Platform GPL34284
Summary
Crotonylation is a crotonyl-coenzyme A (CoA)-mediated post-translational modification best known for its roles in epigenetic regulation. Histone lysine crotonylation (Kcr) has been reported to be involved in tumor-related biological functions such as DNA damage repair and immune infiltration. Here we find that abnormal reduction of histone Kcr significantly correlates with a poor response to epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in resistant models of lung cancer cell lines, and in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. The crotonyl-CoA-producing enzyme ACSS2 is the key regulator of the resistance-related change of crotonylation. Quantitative crotonylomic, transcriptomic and epigenomic analyses reveal that EGFR-TKI resistance is accompanied by reduced levels of histone 3 lysine 56 crotonylation (H3K56cr) on chromatin, which inhibits transcription of HNF1A and activates the PI3K/AKT signaling pathway.
Published in
Activation of epigenetic reprogramming via crotonylation overcomes resistance to EGFR-TKI therapy in lung cancer
Chen S, Zhong M, Wang X et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 41026825 · doi:10.1073/pnas.2509255122
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Also filed as BioProject PRJNA1123725 and SRA study SRP513817. Searching any of these in the dataset finder brings you back here.

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