{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:20:27Z","timestamp":1777944027580,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Ningbo Health Science and Technology Program","award":["2022y39"],"award-info":[{"award-number":["2022y39"]}]},{"name":"Agriculture and social development project of Yinzhou District","award":["2024AS057"],"award-info":[{"award-number":["2024AS057"]}]},{"name":"Natural Science Foundation of Ningbo Municipality","award":["2024J380"],"award-info":[{"award-number":["2024J380"]}]},{"name":"Zhejiang Provincial Medical and Health Science and Technology Plan Project","award":["2022KY1180"],"award-info":[{"award-number":["2022KY1180"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>\n                    Schlafen family member 11 (\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    ), implicated in cancer drug resistance, may improve poly(ADP-ribose) polymerase inhibitor (PARPi) efficacy. This study investigates\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    \u2019s role in epithelial ovarian cancer (EOC) progression and its influence on PARPi sensitivity, particularly in\n                    <jats:italic toggle=\"yes\">BRCA<\/jats:italic>\n                    -wild-type contexts, with a focus on its emerging function in proteostasis regulation.\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    expression in EOC and adjacent tissues was evaluated via immunohistochemistry, quantitative polymerase chain reaction (PCR), and Western blot. Functional assays\u2014including cell viability, transwell migration, wound healing, and colony formation\u2014assessed\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    \u2019s effects on SKOV3 cells (\n                    <jats:italic toggle=\"yes\">BRCA<\/jats:italic>\n                    -wild-type) proliferation and invasiveness. PARPi sensitivity in SKOV3 cells with\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    knockdown or overexpression (OE) was tested using Cell Counting Kit (CCK)-8 and Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assays. Protein stability and ubiquitination levels of\n                    <jats:italic toggle=\"yes\">PARP1\/2<\/jats:italic>\n                    were analyzed as the central mechanism.\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    mRNA and protein levels were markedly lower in EOC tissues compared with normal tissues. Silencing\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    enhanced EOC cell proliferation, migration, and invasion, whereas OE inhibited these malignant behaviors.\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    knockdown reduced PARPi-induced apoptosis and drug sensitivity, while its OE amplified these responses. Mechanistically, we demonstrate that\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    suppresses global proteotoxic ubiquitination, thereby specifically stabilizing PARP1\/2 proteins and potentiating PARPi-mediated DNA damage through enhanced chromatin trapping.\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    enhances PARPi sensitivity in EOC by stabilizing PARP1\/2 via inhibition of proteotoxic ubiquitination, supporting its role as a biomarker in a\n                    <jats:italic toggle=\"yes\">BRCA<\/jats:italic>\n                    -wild-type EOC cell model where PARPi efficacy is limited by intrinsic resistance. While the application of PARPi in other subtypes of EOC still requires further validation,\n                    <jats:italic toggle=\"yes\">SLFN11<\/jats:italic>\n                    may improve PARPi response and could be explored as a strategy to address PARPi resistance.\n                  <\/jats:p>","DOI":"10.1177\/10445498261422919","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T09:55:27Z","timestamp":1773482127000},"page":"226-240","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["SLFN11 Enhances PARPi Sensitivity in Ovarian Cancer via Ubiquitin-Mediated Stabilization"],"prefix":"10.1177","volume":"45","author":[{"given":"Minjie","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laifu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pathology, the Affiliated People\u2019s Hospital of Ningbo University, Ningbo, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101271"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adh7950"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071939"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2022.10.011"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-017-3501-8"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2018-0215"},{"issue":"4","key":"e_1_3_5_8_1","first-page":"215","article-title":"PARP inhibitors: Review of mechanisms of action and BRCA1\/2 mutation targeting","volume":"15","author":"Dziadkowiec KN","year":"2016","unstructured":"Dziadkowiec KN, , G\u0105siorowska E, , Nowak-Markwitz E, et al. PARP inhibitors: Review of mechanisms of action and BRCA1\/2 mutation targeting. Prz Menopauzalny, 2016; 15(4):215\u2013219.","journal-title":"Prz Menopauzalny"},{"key":"e_1_3_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.04.024"},{"key":"e_1_3_5_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf789"},{"key":"e_1_3_5_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13184601"},{"key":"e_1_3_5_12_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60637"},{"key":"e_1_3_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2025.103830"},{"key":"e_1_3_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf086"},{"key":"e_1_3_5_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0207399"},{"issue":"2","key":"e_1_3_5_16_1","first-page":"2328","article-title":"The tumor suppressor OVCA1 is a short half-life protein degraded by the ubiquitin-proteasome pathway","volume":"17","author":"Lin Y","year":"2018","unstructured":"Lin Y, , Kong F, , Li Y, et al. The tumor suppressor OVCA1 is a short half-life protein degraded by the ubiquitin-proteasome pathway. 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