{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:53:54Z","timestamp":1785412434750,"version":"3.56.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P20CA233307"],"award-info":[{"award-number":["P20CA233307"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"publisher","award":["BCRF-20-071"],"award-info":[{"award-number":["BCRF-20-071"]}],"id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01MD013452"],"award-info":[{"award-number":["R01MD013452"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,5,12]]},"abstract":"<jats:p>\n                    Pseudogenes have been regarded as nonfunctional byproducts of evolutionary processes. However, emerging evidence indicates that pseudogenes perform diverse biological roles in human physiology and pathology. We identified the\n                    <jats:italic toggle=\"yes\">BRCA1<\/jats:italic>\n                    pseudogene (\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    ), a fusion pseudogene derived from the\n                    <jats:italic toggle=\"yes\">BRCA1<\/jats:italic>\n                    tumor suppressor and\n                    <jats:italic toggle=\"yes\">RPLP1<\/jats:italic>\n                    ribosomal protein genes, as an immunoregulatory RNA in breast cancer. In this study, we show that\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    expression varies across multiple cancer cell types, with no significant association with\n                    <jats:italic toggle=\"yes\">BRCA1<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">BRCA2<\/jats:italic>\n                    somatic mutations in breast and ovarian tumors. Interestingly,\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    inhibition elicits antitumor effects in multiple cancer cell types and preclinical tumor models through an antiviral defense mechanism. Loss of\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    induces antiviral gene expression, promotes apoptosis, and increases sensitivity to chemotherapy in various cancer cells, without inducing apoptosis in nonmalignant cells. This antiviral response also enhances macrophage-mediated phagocytosis of\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    -deficient cancer cells. Mechanistically, the majority of\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    transcripts are circular RNAs and regulate NF-\u03baB-driven antiviral gene expression. Furthermore, intratumoral expression of\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    is elevated in tumor cells, compared to normal breast tissue, and its depletion significantly inhibits the growth of both primary and metastatic breast tumor organoids. Finally, in a humanized mouse model of breast cancer,\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    loss stimulates antiviral gene expression and increases T cell infiltration into tumors. These findings support a critical role for\n                    <jats:italic toggle=\"yes\">BRCA1P1<\/jats:italic>\n                    in regulating innate immune defense and antitumor responses across cancer types, suggesting that targeting pseudogene-derived RNAs may offer innovative therapeutic strategies to enhance antitumor immunity in breast and other cancers.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2528911123","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:10:45Z","timestamp":1777921845000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Regulation of antiviral and antitumor immunity by the\n                    <i>BRCA1<\/i>\n                    pseudogene in human cancers"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7465-2680","authenticated-orcid":false,"given":"Yoo Jane","family":"Han","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Hematology\/Oncology, Department of Medicine, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3332-8571","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Hematology\/Oncology, Department of Medicine, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9704-1882","authenticated-orcid":false,"given":"Maryam","family":"Shariff","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Hematology\/Oncology, Department of Medicine, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulin","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Hematology\/Oncology, Department of Medicine, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Khramtsova","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Hematology\/Oncology, Department of Medicine, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long Chi","family":"Nguyen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Ben May Department for Cancer Research, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Peiffer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Hematology\/Oncology, Department of Medicine, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nansheng","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lewicka","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Moore","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0541-6270","authenticated-orcid":false,"given":"Joseph A.","family":"Piccirilli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, University of Chicago","place":["Chicago"]},{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9936-1599","authenticated-orcid":false,"given":"Olufunmilayo I.","family":"Olopade","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Section of Hematology\/Oncology, Department of Medicine, University of Chicago","place":["Chicago"]},{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Human Genetics, University of Chicago","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0196-1"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/74184"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201762"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/304501a0"},{"key":"e_1_3_4_5_2","first-page":"1657","article-title":"Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: B-raf-1 encoding the p94Braf\/Rmil and B-raf-2, a processed pseudogene","volume":"7","author":"Eychene A.","year":"1992","unstructured":"A. Eychene, J. V. Barnier, F. Apiou, B. Dutrillaux, G. Calothy, Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: B-raf-1 encoding the p94Braf\/Rmil and B-raf-2, a processed pseudogene. Oncogene 7, 1657\u20131660 (1992).","journal-title":"Oncogene"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/306594a0"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-1959"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01535"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-177808"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.043"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2658311"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1904022116"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008814"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-017-0312-z"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.11.006"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-017-0005-y"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00762"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.011"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1092790"},{"key":"e_1_3_4_20_2","first-page":"2507","article-title":"The 5\u2019 end of the BRCA1 gene lies within a duplicated region of human chromosome 17q21","volume":"12","author":"Brown M. A.","year":"1996","unstructured":"M. A. Brown , The 5\u2019 end of the BRCA1 gene lies within a duplicated region of human chromosome 17q21. Oncogene 12, 2507\u20132513 (1996).","journal-title":"Oncogene"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-008-0256-2"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/339434"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3708"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111171"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00520-5"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.803427"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.035667.112"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-024-00721-7"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaf013"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.046"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp2622"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-120420-125117"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.08.020"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.06.001"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101920"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217769"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70063-4"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac168"},{"key":"e_1_3_4_39_2","unstructured":"M. Shariff BP1. GitHub. https:\/\/github.com\/olopade-lab\/BP1. Deposited 16 April 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2528911123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:11:17Z","timestamp":1777921877000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2528911123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":39,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,5,12]]}},"alternative-id":["10.1073\/pnas.2528911123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2528911123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"assertion":[{"value":"2025-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2528911123"}}