PRMT5-mediated FUBP1 methylation accelerates prostate cancer progression
Strategies beyond hormone-related therapy need to be developed to improve prostate cancer mortality. Here, we show that FUBP1 and its methylation were essential for prostate cancer progression, and a competitive peptide interfering with FUBP1 methylation suppressed the development of prostate cancer. FUBP1 accelerated prostate cancer development in various preclinical models. PRMT5-mediated FUBP1 methylation, regulated by BRD4, was crucial for its oncogenic effect and correlated with earlier biochemical recurrence in our patient cohort. Suppressed prostate cancer progression was observed in various genetic mouse models expressing the FUBP1 mutant deficient in PRMT5-mediated methylation. A competitive peptide, which was delivered through nanocomplexes, disrupted the interaction of FUBP1 with PRMT5, blocked FUBP1 methylation, and inhibited prostate cancer development in various preclinical models. Overall, our findings suggest that targeting FUBP1 methylation provides a potential therapeutic strategy for prostate cancer management.
Authors
- Zengming Wang (ORCID: https://orcid.org/0009-0000-1691-8244)
- Xuebin Zhang (ORCID: https://orcid.org/0000-0001-6001-1498)
- Luonan Chen (ORCID: https://orcid.org/0000-0002-3960-0068)
- Jun Qin (ORCID: https://orcid.org/0000-0002-2263-128X)
- Xiao Hu (ORCID: https://orcid.org/0000-0003-1128-4099)
- Shengsong Huang (ORCID: https://orcid.org/0000-0002-6700-3092)
- Lichen Yin (ORCID: https://orcid.org/0000-0002-4573-0555)
- Weiwei Yan (ORCID: https://orcid.org/0009-0009-2031-3067)
- Denglong Wu (ORCID: https://orcid.org/0009-0008-0398-7337)
- Zhenfei Li (ORCID: https://orcid.org/0000-0001-6520-431X)
- Yang Liu (ORCID: https://orcid.org/0000-0002-0367-8189)
- Jiahui Chen (ORCID: https://orcid.org/0000-0001-9186-1110)
- Kai Xiao (ORCID: https://orcid.org/0000-0002-3070-2789)
- Ping Wu (ORCID: https://orcid.org/0000-0003-1901-195X)
- Li-Ming Sun (ORCID: https://orcid.org/0000-0001-6180-4924)
- Chao Peng
- Xuefeng Qiu
Institutions
- Tongji University (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Soochow University (CN)
- Shanghai Institute of Nutrition and Health (CN)
- Nanjing Drum Tower Hospital (CN)
- Shanghai Advanced Research Institute (CN)
- Center for Excellence in Molecular Cell Science (CN)
- Tongji Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- Nanjing University (CN)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2024-08-15
- DOI
- https://doi.org/10.1172/jci175023
- Citations
- 11
- Primary Topic
- Cancer-related gene regulation
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- Natural Science Foundation of Shanghai
- National Natural Science Foundation of China
- Chinese Academy of Sciences