{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T10:24:07Z","timestamp":1770891847621,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"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":["82104448"],"award-info":[{"award-number":["82104448"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Hydnocarpin D (HD) is a flavonolignan compound isolated from\n Hydnocarpus wightiana<\/jats:italic>\n . This study was to investigate the effect of HD on ovarian cancer mediated by the regulation of\n SERPINE1<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Cytotoxicity was assessed by the MTT assay. Cell migration and invasion were examined using wound healing and Boyden chamber assays. An orthotopic xenograft model was constructed to determine the inhibitory effect of HD on ovarian cancer in vivo. Differential gene expression was screened by RNA sequencing. A 3\u2032\u2010UTR luciferase assay was performed to confirm the regulatory effect of microRNA\u2010145\u20105p on\n SERPINE1<\/jats:italic>\n . Small interfering RNA and microRNA mimics\/inhibitors were introduced to elucidate the mechanism.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n HD inhibited the migration and invasion of SKOV3 and OVCAR4 cells without showing cytotoxic effects. HD inhibited the growth and metastasis of ovarian cancer in vivo. RNA\u2010sequencing analysis suggested that HD suppressed metastasis by inhibiting\n SERPINE1<\/jats:italic>\n expression. Free uPA, which is not bound to PAI\u20101 (\n SERPINE1<\/jats:italic>\n ), was up\u2010regulated, whereas vitronectin, integrin\n \u03b1<\/jats:italic>\n V and phosphorylated FAK, the downstream metastasis\u2010related signalling factors for PAI\u20101, were down\u2010regulated after treatment with HD.\n SERPINE1<\/jats:italic>\n inhibition attenuated the effect of HD on reducing cell migration and rhPAI\u20101 enhanced the effect of HD. We identified microRNA\u2010145\u20105p as the post\u2010transcriptional repressor of\n SERPINE1<\/jats:italic>\n . MicroRNA\u2010145\u20105p was up\u2010regulated by HD, and its overexpression enhanced the inhibition of PAI\u20101 expression and migration by HD, whereas its inhibition had the opposite effect.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Implications<\/jats:title>\n \n We showed that HD inhibits metastasis in ovarian cancer by up\u2010regulating microRNA\u2010145\u20105p, which targets\n SERPINE1<\/jats:italic>\n , inhibiting vitronectin\/integrin\/FAK signalling.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.70251","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T07:42:36Z","timestamp":1762846956000},"page":"1140-1152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydnocarpin D\u2010induced microRNA\u2010145\u20105p down\u2010regulates\n SERPINE1<\/i>\n and suppresses metastasis in ovarian cancer"],"prefix":"10.1111","volume":"183","author":[{"given":"Zhihui","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenjun","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingtao","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenying","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University Hangzhou 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