{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:57:56Z","timestamp":1789480676228,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":202,"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":["82173110"],"award-info":[{"award-number":["82173110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The ubiquitin domain\u2010containing protein 1 (UBTD1) is involved in protein homeostasis and cell cycle regulation, and emerging evidence suggests its role in tumor biology. However, its function in ovarian cancer (OC) remains unclear. OC is highly lethal due to late diagnosis, metastasis, and platinum resistance. This study is aimed at investigating the role of UBTD1 in OC by integrating single\u2010cell transcriptomics, mutation and HRD\u2010related analyses, tumor microenvironment evaluation, and experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined UBTD1 expression, prognosis, somatic mutation features, and immune microenvironment characteristics utilizing public databases, such as the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Single\u2010cell RNA\u2010seq data were analyzed using Seurat, hdWGCNA, and CopyKAT to characterize UBTD1\u2010associated malignant\u2010cell states and inferred CNV burden. Based on the median UBTD1 expression, TCGA\u2010OV samples were divided into high and low expression groups to compare mutation spectra, DNA repair pathway activity, stromal scores, and immune cell infiltration. Functional assays were performed in A2780 and SK\u2010OV\u20103 cell lines following lentiviral shRNAs\u2010mediated UBTD1 knockdown. RNA sequencing and rescue experiments were used to explore downstream pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Integrated single\u2010cell and TCGA\u2010OV analyses revealed that UBTD1\u2010low tumors were enriched for genomic instability\u2013related features, including increased inferred CNV burden and higher tumor mutation burden. By comparison, UBTD1\u2010high tumors showed increased stromal scores and modest enrichment of selected immune\u2010cell populations, including macrophages and neutrophils. Experimentally, UBTD1 was upregulated in OC and associated with poor prognosis. UBTD1 knockdown inhibited malignant phenotypes, enhanced cisplatin sensitivity, promoted apoptosis, and suppressed TNF\/AP\u20101\/FOS\u2013related signaling. FOS overexpression partially reversed the effects of UBTD1 silencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>UBTD1 expression defines distinct mutation and microenvironmental states in OC and functionally promotes malignant phenotypes, potentially through TNF\/AP\u20101\/FOS\u2013related signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/9479429","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:24:51Z","timestamp":1784715891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["UBTD1 Drives Ovarian Cancer Progression via Mutation\u2010Associated Alterations, Stromal Microenvironment Remodeling, and TNF\/AP\u20101 Signaling"],"prefix":"10.1155","volume":"2026","author":[{"given":"Aixin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanying","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-1827","authenticated-orcid":false,"given":"Baiyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6534-6991","authenticated-orcid":false,"given":"Yongbin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5277-4321","authenticated-orcid":false,"given":"Cuiping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21456"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24149"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-01967-3"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2023.0197"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.100355"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-024-01461-w"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-024-01386-4"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/0115748928323408241002131753"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06890-5"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.44789"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14924"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.143473"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-61363-1"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.386"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.10.137"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846570"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13619-026-00285-x"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202500461"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114579"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-025-01533-4"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.7826"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31937"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2014.02.038"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118719"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1677839"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-025-00818-7"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-2952(99)00333-0"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7700409"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4478"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.725473"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.01.039"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2023.102409"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-025-02219-5"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-07575-z"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02924"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04870"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204416"},{"key":"e_1_2_12_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1535-6108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