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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:p>\n                    Androgen receptor (AR) signaling is essential for prostate cancer (PCa) cell growth and remains a key therapeutic target in castration-resistant PCa (CRPC). While circular RNAs (circRNAs) are increasingly recognized as important regulatory molecules, their roles in AR signaling during PCa progression remain poorly understood. This study identified\n                    <jats:italic toggle=\"yes\">circUTRN<\/jats:italic>\n                    , an AR-inhibited circRNA that is upregulated following neoadjuvant hormonal therapy and downregulated in PCa tissues.\n                    <jats:italic toggle=\"yes\">circUTRN<\/jats:italic>\n                    inhibits proliferation in both castration-sensitive and castration-resistant PCa. Mechanistically,\n                    <jats:italic toggle=\"yes\">circUTRN<\/jats:italic>\n                    binds to acetyl-CoA carboxylase 1 (ACC1) and impairs the activity through both phosphorylation-dependent and independent pathways, thereby disturbing de novo fatty acid synthesis. The dynamic relation between\n                    <jats:italic toggle=\"yes\">circUTRN<\/jats:italic>\n                    and ACC1 expression during PCa progression from treatment-na\u00efve to therapeutic-resistant states highlights the metabolic vulnerability of fatty acid synthesis. Notably, we developed nanoparticles to deliver\n                    <jats:italic toggle=\"yes\">circUTRN<\/jats:italic>\n                    in combination with AR signaling inhibitors (ARSIs). This approach effectively suppressed CRPC xenograft tumor growth, even in models resistant to next-generation ARSIs. This study reveals an AR-regulated circRNA involved in PCa progression and suggests a potential therapeutic strategy for treatment-resistant PCa.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2504904123","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T18:43:12Z","timestamp":1767120192000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Circular RNA\u2013based therapy targeting metabolic vulnerability of fatty acid synthesis overcomes castration-resistant prostate cancer"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9881-9561","authenticated-orcid":false,"given":"Yudong","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine","place":["Hangzhou, 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