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Thus, it is still unclear if non-genetic mechanisms are sufficient to trigger malignant transformation. Special AT-rich binding protein 2 (SATB2) is a chromatin organizer that brings distal DNA elements into close proximity, thus remodeling chromatin structures to reprogram cell-specific and\/or developmentally sensitive gene networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we chronically exposed human bronchial lung epithelial cells to \u2264\u20092 \u00b5M inorganic arsenic, and then used biochemical, molecular, and phenotypic assays to understand how changes in\n                      <jats:italic>SATB2<\/jats:italic>\n                      expression and chromatin structure relate to oncogenic transformation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We discovered that\n                      <jats:italic>SATB2<\/jats:italic>\n                      generates a co-expressed\n                      <jats:italic>circ3915<\/jats:italic>\n                      RNA that can be translated into a peptide that co-localizes with SATB2 in and around the nuclear membrane. Ectopic\n                      <jats:italic>SATB2<\/jats:italic>\n                      or\n                      <jats:italic>circ3915<\/jats:italic>\n                      expression rearranged global chromatin accessibility, generated\n                      <jats:italic>KRAS<\/jats:italic>\n                      - and\n                      <jats:italic>NFE2L2<\/jats:italic>\n                      -like oncogenic gene expression patterns, and induced oncogenic phenotypes and KRAS-like transcriptional programs in lung epithelial cells without iAs exposure or engineered driver mutations.\n                      <jats:italic>SATB2<\/jats:italic>\n                      and\n                      <jats:italic>circ3915<\/jats:italic>\n                      transcripts persisted through the epithelial-to-mesenchymal transition and were co-regulated in human LUAD and LUSC tumors and adjacent normal tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study shows that transcriptional programs associated with oncogenic pathways can be activated in differentiated mammalian cells without predisposing mutations in oncogenes or epigenetic regulators.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-026-03021-9","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:25:24Z","timestamp":1782285924000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SATB2 dysregulation generates a novel circular RNA and drives KRAS-like transcriptional reprogramming and transformation-associated phenotypes"],"prefix":"10.1186","volume":"24","author":[{"given":"Rebekah","family":"Eleazer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smitha","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke J.","family":"Shoemaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley N.","family":"Saintilnord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard N.","family":"Cassidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Pyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly T.","family":"Soper-Hopper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoungjoo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell P.","family":"Chandler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne N.","family":"Fondufe-Mittendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"issue":"7381","key":"3021_CR1","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/nature10762","volume":"481","author":"M Greaves","year":"2012","unstructured":"Greaves M, Maley CC. 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