{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:02:34Z","timestamp":1791460954244,"version":"4.3.4"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Oncol"],"DOI":"10.1007\/s12032-026-03380-w","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:45:44Z","timestamp":1791459944000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Silencing the genome: role of HUSH complex in retrotransposon regulation and cancer development"],"prefix":"10.1007","volume":"43","author":[{"given":"Hawaida","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"Tariq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aqsa","family":"Mehreen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran Khan","family":"Yousafzai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"Mahmood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaista","family":"Aslam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma Saleem","family":"Qazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaineb","family":"Akram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rida Fatima","family":"Saeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"3380_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.0014-3820.2001.tb01268.x","volume":"55","author":"MG Kidwell","year":"2001","unstructured":"Kidwell MG, Lisch DR. Perspective: transposable elements, parasitic DNA, and genome evolution. Evolution. 2001;55:1\u201324.","journal-title":"Evolution"},{"key":"3380_CR2","first-page":"32","volume":"1","author":"L Pray","year":"2008","unstructured":"Pray L. Transposons, or jumping genes: Not junk DNA. Nature Education. 2008;1:32.","journal-title":"Nature Education."},{"key":"3380_CR3","first-page":"13","volume":"41","author":"M Gbadegesin","year":"2012","unstructured":"Gbadegesin M. Transposable elements in the genomes: parasites, junks. Afr: J Med med. Sc. 2012;41:13\u201325.","journal-title":"Sc"},{"key":"3380_CR4","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.gde.2016.01.001","volume":"37","author":"P Mita","year":"2016","unstructured":"Mita P, Boeke JD. How retrotransposons shape genome regulation. Curr Opin Genet Dev. 2016;37:90\u2013100.","journal-title":"Curr Opin Genet Dev"},{"key":"3380_CR5","doi-asserted-by":"crossref","unstructured":"Bloor S, Wit N, Lehner PJ. RNA binding by Periphilin plays an essential role in initiating silencing by the HUSH complex. bioRxiv. 2024;602677.","DOI":"10.1101\/2024.07.17.602677"},{"key":"3380_CR6","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1038\/s41586-021-04228-1","volume":"601","author":"I Transgenes Are HUSH-Repressed","year":"2022","unstructured":"Transgenes Are HUSH-Repressed I. Genome surveillance by HUSH-mediated silencing of intronless mobile elements. Nature. 2022;601:441.","journal-title":"Nature"},{"key":"3380_CR7","doi-asserted-by":"publisher","first-page":"596","DOI":"10.3390\/v12060596","volume":"12","author":"K Fukuda","year":"2020","unstructured":"Fukuda K, Shinkai Y. SETDB1-mediated silencing of retroelements. Viruses. 2020;12:596.","journal-title":"Viruses"},{"key":"3380_CR8","doi-asserted-by":"publisher","first-page":"4940","DOI":"10.1038\/s41467-020-18761-6","volume":"11","author":"CH Douse","year":"2020","unstructured":"Douse CH, Tchasovnikarova IA, Timms RT, Protasio AV, Seczynska M, Prigozhin DM, et al. TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control. Nat Commun. 2020;11:4940.","journal-title":"Nat Commun"},{"key":"3380_CR9","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3389\/fmicb.2019.00224","volume":"10","author":"G Chougui","year":"2019","unstructured":"Chougui G, Margottin-Goguet F. HUSH, a link between intrinsic immunity and HIV latency. Front Microbiol. 2019;10:224.","journal-title":"Front Microbiol"},{"key":"3380_CR10","doi-asserted-by":"publisher","first-page":"5387","DOI":"10.1038\/s41467-020-19170-5","volume":"11","author":"H Tunbak","year":"2020","unstructured":"Tunbak H, Enriquez-Gasca R, Tie CH, Gould PA, Mlcochova P, Gupta RK, et al. The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s. Nat Commun. 2020;11:5387.","journal-title":"Nat Commun"},{"key":"3380_CR11","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/carcin\/bgp220","volume":"31","author":"S Sharma","year":"2010","unstructured":"Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31:27\u201336.","journal-title":"Carcinogenesis"},{"key":"3380_CR12","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.jclinepi.2010.04.026","volume":"64","author":"G Guyatt","year":"2011","unstructured":"Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction\u2014GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383\u201394.","journal-title":"J Clin Epidemiol"},{"key":"3380_CR13","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41586-021-03520-4","volume":"595","author":"GK Griffin","year":"2021","unstructured":"Griffin GK, Wu J, Iracheta-Vellve A, Patti JC, Hsu J, Davis T, et al. Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity. Nature. 2021;595:309\u201314.","journal-title":"Nature"},{"key":"3380_CR14","doi-asserted-by":"crossref","unstructured":"Mcgeary MK, Damsky W, Daniels A, Song E, Micevic G, Huet-Calderwood C, Lou HJ, Paradkar S, Kaech S, Calderwood DA. Setdb1-loss induces type-I interferons and immune clearance of melanoma. bioRxiv 2023;23:541922.","DOI":"10.1101\/2023.05.23.541922"},{"key":"3380_CR15","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/s41588-021-00829-8","volume":"53","author":"Z Gu","year":"2021","unstructured":"Gu Z, Liu Y, Zhang Y, Cao H, Lyu J, Wang X, et al. Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia. Nat Genet. 2021;53:672\u201382.","journal-title":"Nat Genet"},{"key":"3380_CR16","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.1016\/j.exphem.2020.09.163","volume":"88","author":"J Xu","year":"2020","unstructured":"Xu J. 2001 \u2013 HUSHING LINE-1 retrotransposition is an epigenetic liability of myeloid leukemias. Exp Hematol. 2020;88:S27.","journal-title":"Exp Hematol"},{"key":"3380_CR17","first-page":"34","volume":"3","author":"D Ardeljan","year":"2018","unstructured":"Ardeljan D. LINE-1 Retrotransposons: a source of replication stress in cancer. Johns Hopkins University. 2018;3:34.","journal-title":"Johns Hopkins University."},{"key":"3380_CR18","doi-asserted-by":"publisher","first-page":"19489","DOI":"10.1074\/jbc.M513249200","volume":"281","author":"H Li","year":"2006","unstructured":"Li H, Rauch T, Chen Z-X, Szab\u00f3 PE, Riggs AD, Pfeifer GP. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem. 2006;281:19489\u2013500.","journal-title":"J Biol Chem"},{"key":"3380_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13072-018-0231-z","volume":"11","author":"T Tsusaka","year":"2018","unstructured":"Tsusaka T, Kikuchi M, Shimazu T, Suzuki T, Sohtome Y, Akakabe M, et al. Tri-methylation of ATF7IP by G9a\/GLP recruits the chromodomain protein MPP8. Epigenetics Chromatin. 2018;11:1\u201316.","journal-title":"Epigenetics Chromatin"},{"key":"3380_CR20","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948297","volume":"20","author":"T Tsusaka","year":"2019","unstructured":"Tsusaka T, Shimura C, Shinkai Y. ATF7IP regulates SETDB1 nuclear localization and increases its ubiquitination. EMBO Rep. 2019;20:e48297.","journal-title":"EMBO Rep"},{"key":"3380_CR21","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1158\/1078-0432.CCR-24-2669","volume":"31","author":"M Michel","year":"2025","unstructured":"Michel M, Heidary M, Mechri A, DA Silva K, Gorse M, Dixon V, et al. Noninvasive multicancer detection using DNA hypomethylation of LINE-1 retrotransposons. Clin Cancer Res. 2025;31:1275\u201391.","journal-title":"Clin Cancer Res"},{"key":"3380_CR22","doi-asserted-by":"publisher","first-page":"55098","DOI":"10.18632\/oncotarget.10398","volume":"7","author":"K Mima","year":"2016","unstructured":"Mima K, Nowak JA, Qian ZR, Cao Y, Song M, Masugi Y, et al. Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival. Oncotarget. 2016;7:55098.","journal-title":"Oncotarget"},{"key":"3380_CR23","doi-asserted-by":"publisher","first-page":"3730","DOI":"10.1016\/j.celrep.2018.05.090","volume":"23","author":"TH Nguyen","year":"2018","unstructured":"Nguyen TH, Carreira PE, Sanchez-Luque FJ, Schauer SN, Fagg AC, Richardson SR, et al. L1 retrotransposon heterogeneity in ovarian tumor cell evolution. Cell Rep. 2018;23:3730\u201340.","journal-title":"Cell Rep"},{"key":"3380_CR24","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.2217\/epi-2019-0091","volume":"11","author":"S Tahara","year":"2019","unstructured":"Tahara S, Tahara T, Horiguchi N, Okubo M, Terada T, Yoshida D, et al. Lower LINE-1 methylation is associated with promoter hypermethylation and distinct molecular features in gastric cancer. Epigenomics. 2019;11:1651\u20139.","journal-title":"Epigenomics"},{"key":"3380_CR25","doi-asserted-by":"publisher","first-page":"7534","DOI":"10.1038\/s41467-024-50765-4","volume":"15","author":"N Pandiloski","year":"2024","unstructured":"Pandiloski N, Horvath V, Karlsson O, Koutounidou S, Dorazehi F, Christoforidou G, et al. DNA methylation governs the sensitivity of repeats to restriction by the HUSH-MORC2 corepressor. Nat Commun. 2024;15:7534.","journal-title":"Nat Commun"},{"key":"3380_CR26","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1101\/gr.228171.117","volume":"28","author":"L Robbez-Masson","year":"2018","unstructured":"Robbez-Masson L, Tie CH, Conde L, Tunbak H, Husovsky C, Tchasovnikarova IA, et al. The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes. Genome Res. 2018;28:836\u201345.","journal-title":"Genome Res"},{"key":"3380_CR27","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1016\/j.molcel.2022.03.004","volume":"82","author":"W Garland","year":"2022","unstructured":"Garland W, M\u00fcller I, Wu M, Schmid M, Imamura K, Rib L, et al. Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression. Mol Cell. 2022;82:1691\u2013707.","journal-title":"Mol Cell"},{"key":"3380_CR28","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez TC, Yurkovetskiy L, Nagalekshmi K, Lam CHO, Jazbec E, Maitland SA, Wolfe SA, Sontheimer EJ, Luban J. PRC1. 6 localizes on chromatin with the human silencing hub (HUSH) complex for promoter-specific silencing. bioRxiv;2024","DOI":"10.1101\/2024.07.12.603173"},{"key":"3380_CR29","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1021\/acschembio.1c00429","volume":"16","author":"JM Waybright","year":"2021","unstructured":"Waybright JM, Clinkscales SE, Barnash KD, Budziszewski GR, Rectenwald JM, Chiarella AM, et al. A peptidomimetic ligand targeting the chromodomain of MPP8 reveals HRP2\u2019s association with the HUSH complex. ACS Chem Biol. 2021;16:1721\u201336.","journal-title":"ACS Chem Biol"}],"container-title":["Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-026-03380-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12032-026-03380-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-026-03380-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:45:46Z","timestamp":1791459946000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12032-026-03380-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":29,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,11]]}},"alternative-id":["3380"],"URL":"https:\/\/doi.org\/10.1007\/s12032-026-03380-w","relation":{},"ISSN":["1559-131X"],"issn-type":[{"value":"1559-131X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"7 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors hereby claim that they have no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"323"}}