Anti-tumor activity of CDYL2b in prostate cancer

Area of Science:

• Oncology
• Epigenetics
• Molecular Biology

Background:

• Prostate cancer remains a significant cause of male mortality, with its molecular drivers incompletely understood.
• Histone demethylases JMJD2A and JMJD2B are implicated in prostate tumorigenesis.
• The epigenetic reader gene CDYL2's role in prostate cancer is largely unexplored.

Purpose of the Study:

• To investigate the role of CDYL2 and its isoforms in prostate cancer.
• To elucidate the regulatory relationship between JMJD2A/JMJD2B and CDYL2.
• To identify potential therapeutic targets for prostate cancer treatment.

Main Methods:

• Bioinformatic analysis of CDYL2 expression in prostate tumors.
• Characterization of CDYL2 isoforms and their interaction with chromatin.
• In vitro and in vivo experiments involving CDYL2b overexpression and downregulation in prostate cancer cell lines and xenografts.
• RNA sequencing to identify CDYL2b-regulated genes.
• Co-immunoprecipitation assays to study protein interactions.

Main Results:

• Low CDYL2 expression correlates with increased metastasis, recurrence, and reduced survival in prostate cancer patients.
• Only the CDYL2b isoform is significantly expressed in prostate cancer cells and associates with chromatin.
• CDYL2b overexpression inhibits prostate cancer cell growth and tumor expansion, while downregulation promotes growth.
• CDYL2b upregulates transcription factors HES7, KLF17, and TBX6, which exhibit anti-oncogenic properties.
• JMJD2B, but not JMJD2A, forms complexes with CDYL2b and antagonizes its ability to upregulate HES7 transcription.

Conclusions:

• CDYL2b functions as a tumor suppressor in prostate cancer, potentially through the induction of HES7, KLF17, and TBX6.
• JMJD2A and JMJD2B promote prostate tumorigenesis partly by inhibiting CDYL2b transcription or activity.
• The developmental transcription factors TBX6 and HES7 may also possess tumor-suppressive functions in prostate cancer.