{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:29:24Z","timestamp":1783034964794,"version":"3.54.6"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","issue":"3","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>Decitabine (DAC), a DNA methyltransferase inhibitor (DNMTi), is clinically effective in hematological malignancies such as myelodysplastic syndrome and acute myeloid leukemia, but its precise antineoplastic mechanisms remain incompletely understood. Beyond promoter demethylation, DAC is known to activate endogenous retroviruses (ERVs) and trigger type I interferon (IFN-I) responses, a phenomenon known as viral mimicry. The aim of this study was to investigate the roles of the mouse mammary tumor virus (MMTV) and interferon-\u03b2 (IFN-\u03b2) in DAC-mediated tumor suppression. We employed two murine tumor models\u20144T1 mammary carcinoma and MC38 colon adenocarcinoma\u2014in syngeneic immunocompetent mice, immunodeficient nude mice, and in vitro cultures. RNA and protein expression were assessed by quantitative PCR and immunoblotting, while functional contributions of MMTV and IFN-\u03b2 were tested using short hairpin RNA (shRNA) knockdowns. DAC treatment suppressed tumor growth and pulmonary metastasis in vivo and inhibited cancer cell proliferation in vitro. It induced transcription of MMTV and expression of IFN-\u03b2, with a strong negative correlation between MMTV Env protein levels and tumor mass. Knockdown of either MMTV or IFN-\u03b2 conferred resistance to DAC, confirming their functional roles. Reciprocal regulation was observed: MMTV knockdown reduced IFN-\u03b2 expression, while IFN-\u03b2 knockdown increased MMTV Env accumulation. Furthermore, DAC upregulated interferon regulatory factor 7 (IRF7), but this effect declined during prolonged treatment, suggesting a temporally restricted therapeutic window. In conclusion, our findings provide in vivo support for the viral mimicry hypothesis and demonstrate that MMTV and IFN-\u03b2 contribute to DAC-mediated tumor suppression. The observed IRF7 downregulation and potential induction of immune checkpoints highlight the importance of therapeutic strategies combining DNMTis with immune checkpoint blockade to sustain antineoplastic efficacy.\n\u00a0<\/jats:p>","DOI":"10.17305\/bb.2025.12852","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T22:00:36Z","timestamp":1756332036000},"page":"424-432","source":"Crossref","is-referenced-by-count":3,"title":["Decitabine suppresses tumor growth by activating mouse mammary tumor virus and interferon-\u03b2 pathways"],"prefix":"10.17305","volume":"26","author":[{"given":"Ryan","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0033-5526","authenticated-orcid":false,"given":"Andrew","family":"Brola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cade","family":"Wycoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Wycoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2251-9444","authenticated-orcid":false,"given":"Seth","family":"Neumeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Tuttle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Light","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingguang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6922","published-online":{"date-parts":[[2025,8,27]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/12852\/3991","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/12852\/3991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T22:04:07Z","timestamp":1760393047000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/12852"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,10,11]]}},"URL":"https:\/\/doi.org\/10.17305\/bb.2025.12852","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8,27]]}}}