{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:32:26Z","timestamp":1786692746416,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":225,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31370129"],"award-info":[{"award-number":["31370129"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["GK202302003"],"award-info":[{"award-number":["GK202302003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Breast Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Breast cancer is the most abundant cancer type in female. Genome\u2010wide association study suggests that rs2016394, one SNP at the intron of DLX2 divergent transcript (\n                      <jats:italic>DLX2-DT<\/jats:italic>\n                      ), is significantly associated with this disease. Through 1000 genomes project data analysis, it is observed that another three SNPs, rs743605, rs2357322, and rs17726078, show strong linkage disequilibrium with rs2016394. However, the functional SNP(s) and mechanism are still unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Functional genomics effort was performed for this locus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Through luciferase assay, it is disclosed that rs743605 and rs2016394 are not with the ability to alter gene expression. In contrast, rs2357322 and rs17726078 alleles present significantly different luciferase expression, thus suggesting that these two SNPs are functional mutations. Chromosome conformation capture indicates that\n                      <jats:italic>DLX2<\/jats:italic>\n                      (distal\u2010less Homeobox 2) can interact with the\n                      <jats:italic>cis<\/jats:italic>\n                      \u2010regulatory element containing these two SNPs and should be the regulatory target. Chromatin immunoprecipitation suggests that transcription factor MYC (MYC proto\u2010oncogene, bHLH transcription factor) can bind the rs17726078 surrounding region. Knock\u2010out of the segment containing these two SNPs by CRISPR\/Cas9 can significantly increase\n                      <jats:italic>DLX2<\/jats:italic>\n                      mRNA and protein expression, cell proliferation, colony formation, migration, and wound healing, thus suggesting that the\n                      <jats:italic>cis<\/jats:italic>\n                      \u2010regulatory element is an attenuator for gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      rs2357322 and rs17726078 might influence\n                      <jats:italic>DLX2<\/jats:italic>\n                      expression and further contribute to breast cancer risk.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/tbj\/3096873","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:13:12Z","timestamp":1786691592000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["rs2357322 and rs17726078 Contribute to Breast Cancer Risk by Regulating\n                    <i>DLX2<\/i>\n                    Expression"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4081-0472","authenticated-orcid":false,"given":"Xin-Xin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4088-4882","authenticated-orcid":false,"given":"Hao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8548-6314","authenticated-orcid":false,"given":"Hai-Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8966-9301","authenticated-orcid":false,"given":"Xi-Ting","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5718-0835","authenticated-orcid":false,"given":"Hong-Li","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0671-2222","authenticated-orcid":false,"given":"Jiang-Wei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9904-2561","authenticated-orcid":false,"given":"Yu-Hang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8160-4310","authenticated-orcid":false,"given":"Ru-Hui","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9707-6050","authenticated-orcid":false,"given":"Ru","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2094-0977","authenticated-orcid":false,"given":"Chun-Chun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2425-9485","authenticated-orcid":false,"given":"Chang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/grf.0000000000000239"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2025.101268"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/bab.2769"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.971288"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58789-0"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2023.147676"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-5133-8"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgt404"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.10.012"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03411-9"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.epi-17-1144"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2563"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv260"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2022.8270"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08903"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17811-2"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0481oc"},{"key":"e_1_2_12_19_2","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1038\/emboj.2011.319","article-title":"Transcription Factor Dlx2 Protects From TGFbeta-Induced Cell-Cycle Arrest and Apoptosis","volume":"30","author":"Yilmaz M.","year":"2011","journal-title":"EMBO Journal"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.2874"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.144564"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108272"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.271445.115"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13123005"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2016.06.003"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-649"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.4.7.661"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.09.010"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.292"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clbc.2018.09.004"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-6-114"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.4956"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3242"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004285"}],"container-title":["The Breast Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/tbj\/3096873","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/tbj\/3096873","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/tbj\/3096873","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:13:14Z","timestamp":1786691594000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/tbj\/3096873"}},"subtitle":[],"editor":[{"given":"Karuna","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/tbj\/3096873"],"URL":"https:\/\/doi.org\/10.1155\/tbj\/3096873","archive":["Portico"],"relation":{},"ISSN":["1075-122X","1524-4741"],"issn-type":[{"value":"1075-122X","type":"print"},{"value":"1524-4741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"3096873"}}