{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:55:32Z","timestamp":1790034932842,"version":"4.0.1"},"reference-count":85,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014175","name":"Shanghai Municipal Health and Family Planning Commission","doi-asserted-by":"publisher","award":["2020YJZX0202"],"award-info":[{"award-number":["2020YJZX0202"]}],"id":[{"id":"10.13039\/501100014175","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014175","name":"Shanghai Municipal Health and Family Planning Commission","doi-asserted-by":"publisher","award":["SHDC12020108"],"award-info":[{"award-number":["SHDC12020108"]}],"id":[{"id":"10.13039\/501100014175","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008750","name":"Shanghai ShenKang Hospital Development Center","doi-asserted-by":"publisher","award":["2020YJZX0202"],"award-info":[{"award-number":["2020YJZX0202"]}],"id":[{"id":"10.13039\/501100008750","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008750","name":"Shanghai ShenKang Hospital Development Center","doi-asserted-by":"publisher","award":["SHDC12020108"],"award-info":[{"award-number":["SHDC12020108"]}],"id":[{"id":"10.13039\/501100008750","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies. Currently, no suitable model exists to elucidate the role of RAD51D in disease initiation and progression. Here, we established organoids from primary human FTE and introduced TP53 as well as RAD51D knockdown to enable the exploration of their mutational impact on FTE lesion generation. We observed that TP53 deletion rescued the adverse effects of RAD51D deletion on the proliferation, stemness, senescence, and apoptosis of FTE organoids. RAD51D deletion impaired the homologous recombination (HR) function and induced G2\/M phase arrest, whereas concurrent TP53 deletion mitigated G0\/G1 phase arrest and boosted DNA replication when combined with RAD51D mutation. The co-deletion of TP53 and RAD51D downregulated cilia assembly, development, and motility, but upregulated multiple HGSOC-associated pathways, including the IL-17 signaling pathway. IL-17A treatment significantly improved cell viability. TP53 and RAD51D co-deleted organoids exhibited heightened sensitivity to platinum, poly-ADP ribose polymerase inhibitors (PARPi), and cell cycle-related medication. In summary, our research highlighted the use of FTE organoids with RAD51D mutations as an invaluable in vitro platform for the early detection of carcinogenesis, mechanistic exploration, and drug screening.<\/jats:p>","DOI":"10.3390\/ijms25020886","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T05:24:12Z","timestamp":1704950652000},"page":"886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro"],"prefix":"10.3390","volume":"25","author":[{"given":"Yilin","family":"Dai","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Gao","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranran","family":"Chai","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-6500","authenticated-orcid":false,"given":"Chong","family":"Lu","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Kang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/S0140-6736(18)32552-2","article-title":"Epithelial ovarian cancer","volume":"393","author":"Lheureux","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1001\/jama.2017.21421","article-title":"Screening for Ovarian Cancer","volume":"319","author":"Henderson","year":"2018","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3322\/caac.21559","article-title":"Epithelial ovarian cancer: Evolution of management in the era of precision medicine","volume":"69","author":"Lheureux","year":"2019","journal-title":"CA Cancer J. 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