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Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic inflammation exerts paradoxical effects in breast cancer, inducing growth arrest while sustaining tumor progression. However, how autocrine and paracrine inflammatory cytokine induced senescence integrates with tumor-promoting behaviour remains unclear. Here, we identify a reciprocal IL-1\u03b2\/IL-6 circuit that links inflammatory cues, epigenetic remodeling and cytokine induced senescence in luminal breast cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following treatment with IL-1\u03b2 and IL-6, MCF-7 cells were examined using cell-cycle, apoptosis, reactive oxygen species flow cytometry assays, and senescence assays; RNA sequencing; global DNA methylation quantification; methylation-specific PCR; ChIP-qPCR for histone marks; cytokine ELISA; and western blotting for DNMTs and STAT3\/AKT\/NF-\u03baB signaling proteins. The kinetics of IL-1\u03b2 and IL-6 signaling were examined using receptor antagonism and pharmacological inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL-1\u03b2 induced senescence characterized by G\n                      <jats:sub>0<\/jats:sub>\n                      \/G\n                      <jats:sub>1<\/jats:sub>\n                      arrest, elevated SA-\u03b2-gal activity, ROS accumulation and absence of apoptosis. Transcriptomic profiling revealed cell-cycle regulator repression, enrichment of senescence-associated signatures and a pro-inflammatory secretory phenotype. Mechanistically, IL-1\u03b2 induced increased DNMT1 and DNMT3A expression, elevated global DNA methylation, induced promoter-specific DNA methylation (\n                      <jats:italic>IL-15<\/jats:italic>\n                      ,\n                      <jats:italic>HMGB2<\/jats:italic>\n                      ) and histone mark remodeling (\n                      <jats:italic>IL-6<\/jats:italic>\n                      ,\n                      <jats:italic>IL1RN<\/jats:italic>\n                      ,\n                      <jats:italic>BCL2<\/jats:italic>\n                      ,\n                      <jats:italic>BAX<\/jats:italic>\n                      ) at inflammatory, senescence, and apoptotic loci. IL-1 receptor antagonism attenuated these effects. IL-6 induced downstream of IL-1\u03b2, in turn activated STAT3, increased DNMT1 and DNMT3B expression, amplified IL-1\u03b2 expression and tumor-promoting phenotypes, while sustaining the IL-1\u03b2 induced senescence state. IL-6R blockade disrupted this axis and reduced tumor-promoting effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>An IL-1\u03b2\/IL-6 inflammatory loop drives epigenetic remodeling associated with cytokine induced senescence while promoting tumor-supportive signaling. IL-1\u03b2 initiates the senescence program, whereas IL-6 reinforces and sustains this state through STAT3\/DNMT signaling, highlighting inflammatory cytokine signaling pathways as potential therapeutic targets for breast cancer therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-026-02391-7","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:19:43Z","timestamp":1792271983000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-1\u03b2\/IL-6 inflammatory crosstalk drives DNA methylation and histone remodeling associated with cytokine induced senescence in luminal breast cancer"],"prefix":"10.1007","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1089-0433","authenticated-orcid":false,"given":"Satyajit","family":"Dey Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-0066","authenticated-orcid":false,"given":"Kanaka Sai Ram","family":"Padam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6748-3412","authenticated-orcid":false,"given":"Padival","family":"Shruptha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Atreya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1310-5480","authenticated-orcid":false,"given":"Manjunath B.","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2368-5490","authenticated-orcid":false,"given":"Kapaettu","family":"Satyamoorthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,17]]},"reference":[{"key":"2391_CR1","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.mce.2013.06.003","volume":"382","author":"X Jiang","year":"2014","unstructured":"Jiang X, Shapiro DJ. 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