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Targeting m6A-SCG2-TAMs axis overcomes 5-FU resistance in colorectal cancer via a multi-omics model

2026-07-03Artigo científico Acesso aberto
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dc.contributor.authorSun, Yiming
dc.contributor.authorPeng, Ke
dc.contributor.authorLi, Yuening
dc.contributor.authorZheng, Daofeng
dc.contributor.authorLiu, Ling
dc.contributor.authorYin, Jiuheng
dc.contributor.authorYu, Kun
dc.contributor.authorXu, Cong
dc.contributor.authorConde, João
dc.contributor.authorLi, Zhixi
dc.contributor.authorYin, Chengliang
dc.contributor.authorWang, Wensheng
dc.contributor.authorXiao, Weidong
dc.contributor.institutionCentre for Toxicogenomics and Human Health (ToxOmics)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblNature Publishing Group
dc.date.accessioned2026-07-15T10:18:01Z
dc.date.available2026-07-15T10:18:01Z
dc.date.issued2026-07-03
dc.description© 2026. The Author(s).
dc.description.abstractChemoresistance to 5-fluorouracil (5-FU) remains a critical barrier in colorectal cancer (CRC) management. This study integrates multi-omics data from 26,192 human samples to elucidate the RNA methylation-mediated crosstalk between tumor-associated macrophages (TAMs) and tumor cells. Machine learning models were able to effectively stratify patients by risk and identified a core signature of six genes (including SCG2), whose expression patterns were associated with poor prognosis and chemotherapy resistance-related phenotypes. Mechanistically, 5-FU elevates m6A modification in TAMs, polarizing them toward the M2 phenotype. SCG2 mRNA methylation promotes TNF-α ubiquitination, reducing its levels and thereby sustaining NF-κB activation in tumor cells to drive PCD resistance. The core candidate genes (CCGs) model effectively predicts survival outcomes. Targeting SCG2 represents a novel strategy to reverse chemoresistance by disrupting TAMs-tumor crosstalk, offering actionable targets for personalized therapy optimization.en
dc.description.versionauthorsversion
dc.description.versionepub_ahead_of_print
dc.format.extent82436562
dc.identifier.doi10.1038/s41746-026-02920-y
dc.identifier.issn2398-6352
dc.identifier.otherPURE: 168141342
dc.identifier.otherPURE UUID: d0910d4c-e2fc-432a-abe3-e3eb34586b7f
dc.identifier.otherPubMed: 42399406
dc.identifier.urihttp://hdl.handle.net/10362/204530
dc.language.isoeng
dc.peerreviewedyes
dc.subjectSDG 3 - Good Health and Well-being
dc.titleTargeting m6A-SCG2-TAMs axis overcomes 5-FU resistance in colorectal cancer via a multi-omics modelen
dc.typejournal article
degois.publication.titlenpj Digital Medicine
dspace.entity.typePublication
rcaap.rightsopenAccess

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