biostudies-literatureGu RNCI NIH HHSNIGMS NIH HHS217987https://www.ebi.ac.uk/biostudies/studies/S-EPMC12401169biostudies-literatureUnknown632Prostate cancer is a leading cause of death among men, yet the molecular underpinnings of this malignancy are still not fully understood. We discovered that two histone demethylases driving prostate tumorigenesis, the JMJD2A and JMJD2B enzymes, suppressed transcription of the CDYL2 epigenetic reader gene. Bioinformatic analyses showed that low CDYL2 expression in prostate tumors was associated with more metastasis and disease recurrence as well as reduced survival. Out of the four predicted CDYL2 isoforms, all of which were capable of forming homo- and heteromers, only CDYL2b was appreciably expressed in prostate cancer cells and tightly associated with chromatin. Overexpression of CDYL2b in human DU145 and 22Rv1 prostate cancer cells decreased their growth and clonogenic activity in vitroCancer lettersAnti-tumor activity of CDYL2b in prostate cancer.PMC12401169R03 CA223615R01 CA154745P30 CA225520P30 GM154635Janknecht JGu RJiang HOh SJanknecht RfalseAnti-tumor activity of CDYL2b in prostate cancer.Prostate cancer is a leading cause of death among men, yet the molecular underpinnings of this malignancy are still not fully understood. We discovered that two histone demethylases driving prostate tumorigenesis, the JMJD2A and JMJD2B enzymes, suppressed transcription of the CDYL2 epigenetic reader gene. Bioinformatic analyses showed that low CDYL2 expression in prostate tumors was associated with more metastasis and disease recurrence as well as reduced survival. Out of the four predicted CDYL2 isoforms, all of which were capable of forming homo- and heteromers, only CDYL2b was appreciably expressed in prostate cancer cells and tightly associated with chromatin. Overexpression of CDYL2b in human DU145 and 22Rv1 prostate cancer cells decreased their growth and clonogenic activity in vitro2025-01-01T00:00:00Z2025 Aug2026-05-29T09:33:48.006Z2026-05-19T03:06:55.863ZS-EPMC124011694081271910.1016/j.canlet.2025.217987