YTHDF3 Regulates the Degradation and Stability of m6A‐Enriched Transcripts to Facilitate the Progression of Castration‐Resistant Prostate Cancer
RNA N6-methyladenosine (m6A) readers mediate cancer progression. However, the functional role and potential mechanisms of the m6A readers in prostate cancer tumorigenicity remain to be elucidated. In this study, we demonstrate that YTHDF3 expression is elevated in castration-resistant prostate cancer (CRPC) and positively correlated to high grade, bone metastasis and poor survival. YTHDF3 expression promoted CRPC cell proliferation, epithelial to mesenchymal transition (EMT) and tumour progression. Mechanistically, YTHDF3 promoted the RNA degradation of SPOP and NXK3.1 but stabilized RNA expressions of TWIST1 and SNAI2 dependent on m6A to facilitate cell proliferation and EMT. Additionally, YTHDF3 expression enhanced AKT activity via degrading SPOP in an m6A-dependent manner. Importantly, we found that melatonin can compete with m6A to occupy the m6A-binding cage of YTHDF3, leading to inhibition of YTHFD3 and its target expressions as well as CRPC tumour growth. Our findings uncover an essential role of YTHDF3 in the progression of CRPC and highlight the role of melatonin in anti-CRPC activity.
Authors
- ChangXue Wu
- Hongmei Zeng (ORCID: https://orcid.org/0000-0003-3999-3081)
- Daogui Fan
- Yu‐Hui Peng (ORCID: https://orcid.org/0000-0002-1866-4679)
- Yan Xiao (ORCID: https://orcid.org/0000-0003-4242-6387)
- Jie Xiang (ORCID: https://orcid.org/0000-0001-8937-3564)
- Qifang Zhang
- Tengxiang Chen (ORCID: https://orcid.org/0000-0001-6907-1374)
- Yi Li (ORCID: https://orcid.org/0000-0002-3089-9980)
- Xin Xie (ORCID: https://orcid.org/0009-0004-5343-4010)
- Xiaolan Qi (ORCID: https://orcid.org/0000-0002-9108-6772)
- Jing Zhou (ORCID: https://orcid.org/0000-0003-3780-6107)
- Jingui Duan (ORCID: https://orcid.org/0000-0002-8218-1487)
- Wei Hong (ORCID: https://orcid.org/0000-0002-3317-9401)
- Yan He (ORCID: https://orcid.org/0000-0001-7346-6758)
- Hua Bai (ORCID: https://orcid.org/0000-0003-1979-3760)
- Pingping Chen (ORCID: https://orcid.org/0000-0002-8027-4620)
- Wenfeng Yu
- Wenli Fu
- Tao Li (ORCID: https://orcid.org/0009-0006-6811-2182)
- Jingdi Bai
- Hui Song (ORCID: https://orcid.org/0000-0001-6804-3232)
- Ting Zhang (ORCID: https://orcid.org/0000-0001-5676-4825)
Institutions
- Guiyang Medical University (CN)
- Guizhou University (CN)
- Affiliated Hospital of Guizhou Medical University (CN)
- Second Hospital of Tianjin Medical University (CN)
- Guizhou Provincial People's Hospital (CN)
- Tianjin Medical University (CN)
Publication Details
- Journal
- Journal of Pineal Research
- Published
- 2024-08-01
- DOI
- https://doi.org/10.1111/jpi.13003
- Citations
- 11
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- National Natural Science Foundation of China