{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:57:11Z","timestamp":1790621831951,"version":"4.1.0"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":59,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01CA256741,R01CA278832,R01CA285684,R01CA300246"],"award-info":[{"award-number":["R01CA256741,R01CA278832,R01CA285684,R01CA300246"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:p>\n                    N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A), the most predominant RNA modification in humans, participates in various fundamental and pathological bioprocesses. Dynamic manipulation of m\n                    <jats:sup>6<\/jats:sup>\n                    A deposition in the transcriptome is critical for cancer progression, though how this regulation is achieved remains understudied. Here, we report that, in prostate cancer (PCa), Polycomb group (PcG) protein Enhancer of Zeste Homolog 2 (EZH2) exerts an additional function in m\n                    <jats:sup>6<\/jats:sup>\n                    A regulation via its enzymatic activity. Mechanistically, EZH2 methylates and stabilizes FOXA1 proteins from degradation, which, in turn, facilitates the transcription of m\n                    <jats:sup>6<\/jats:sup>\n                    A reader YTHDF1. Through activating an m\n                    <jats:sup>6<\/jats:sup>\n                    A autoregulation pathway, YTHDF1 enhances the translation of METTL14 and WTAP, 2 critical components of the m\n                    <jats:sup>6<\/jats:sup>\n                    A methyltransferase complex (MTC), and thereby upregulates the global m\n                    <jats:sup>6<\/jats:sup>\n                    A level in PCa cells. We further demonstrate that inhibiting the catalytic activity of EZH2 suppresses the translation process globally through targeting the YTHDF1-m\n                    <jats:sup>6<\/jats:sup>\n                    A axis. By disrupting both the expression and interaction of key m\n                    <jats:sup>6<\/jats:sup>\n                    A MTC subunits, combinational treatment of EZH2 degrader MS8815 and m\n                    <jats:sup>6<\/jats:sup>\n                    A inhibitor STM2457 mitigates prostate tumor growth synergistically. Together, our study decodes a previously hidden interrelationship between EZH2 and mRNA modification, which may be leveraged to advance the EZH2-targeting curative strategies in cancer.\n                  <\/jats:p>","DOI":"10.1172\/jci195840","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T17:00:48Z","timestamp":1763485248000},"source":"Crossref","is-referenced-by-count":6,"title":["EZH2 crosstalk with RNA methylation promotes prostate cancer progression through modulation of m6A autoregulation pathway"],"prefix":"10.1172","volume":"136","author":[{"given":"Yang","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Urology and"},{"name":"Robert H. 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