Abstract | BACKGROUND: METHODS: The expression of NSUN2 and its clinicopathological impact were evaluated in PCa cohorts. The effect of NSUN2 on the biological characteristics of PCa cells was investigated on the basis of gain-offunction and loss-of-function analyses. Subcutaneous models further uncovered the role of NSUN2 in tumor growth. Epi-transcriptome assays with RNA bisulfite sequencing ( RNA-BisSeq) analysis and in vitro enzyme reaction assays were performed to validate the targeted effect of NSUN2 on AR. AR-binding sites in the NSUN2 promoter were investigated by ChIP and luciferase assays to uncover the interplay between NSUN2 and AR signaling. RIP-qPCR and EMSA methods were performed to confirm that YBX1 binds to AR m5 C sites. RESULTS: NSUN2 is highly expressed in PCa and predicts poor outcome. NSUN2 plays roles as a PCa oncogene both in vitro and in vivo. Depletion of NSUN2 results in decreased expression and activities of AR, including AR-V7. Mechanistically, NSUN2 posttranscriptionally stabilized AR by cluster m5 C modification in a m5CYBX1-dependent manner. Strikingly, treatment with enzalutamide, an effective AR inhibitor, reduces NSUN2 expression and decreases the m5C modification level in prostate cancer cells. Finally, we found that AR transcriptionally regulates NSUN2. CONCLUSION:
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Authors | Wenkai Zhu, Fangning Wan, Wenhao Xu, Zheng Liu, Junjie Wang, Hena Zhang, Shenglin Huang, Dingwei Ye |
Journal | Clinical and translational medicine
(Clin Transl Med)
Vol. 12
Issue 9
Pg. e1028
(09 2022)
ISSN: 2001-1326 [Electronic] United States |
PMID | 36169095
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. |
Chemical References |
- AR protein, human
- Androgen Antagonists
- Androgen Receptor Antagonists
- Androgens
- RNA, Messenger
- Receptors, Androgen
- 5-Methylcytosine
- Methyltransferases
- NSUN2 protein, human
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Topics |
- 5-Methylcytosine
- Androgen Antagonists
(pharmacology, therapeutic use)
- Androgen Receptor Antagonists
(pharmacology, therapeutic use)
- Androgens
(metabolism, therapeutic use)
- Epigenesis, Genetic
(genetics)
- Humans
- Male
- Methyltransferases
(genetics, metabolism, therapeutic use)
- Prostatic Neoplasms, Castration-Resistant
(drug therapy, genetics, pathology)
- RNA, Messenger
- Receptors, Androgen
(chemistry, genetics, metabolism)
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