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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
METTL3 Promotes Castration-Resistant Prostate Cancer Progression by Enhancing AKR1C3 Expression
Qihong Nie1, Xiaoyuan Wu2, Xin Huang2
1Department of Oncology, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, China.
Journal of Biochemical and Molecular Toxicology
|June 28, 2026
Summary
N6-methyladenosine (m6A) methyltransferases, particularly METTL3, drive castration-resistant prostate cancer (CRPC) by increasing AKR1C3 expression. Targeting the METTL3/AKR1C3 pathway offers a promising therapeutic strategy for CRPC.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Castration-resistant prostate cancer (CRPC) represents an advanced, lethal stage of prostate cancer (PC).
- N6-methyladenosine (m6A) methyltransferases play critical roles in cancer progression, but their specific functions in CRPC remain underexplored.
Purpose of the Study:
- To investigate the functional roles and underlying molecular mechanisms of m6A methyltransferases in CRPC.
- To identify key m6A regulators implicated in CRPC pathogenesis.
Main Methods:
- Analysis of transcriptomic datasets (GEO, TCGA) to identify dysregulated m6A methyltransferases.
- In vitro assays (cell proliferation, migration, invasion) and in vivo xenograft models to assess the effects of METTL3 knockdown.
- Molecular analyses including western blot, RT-qPCR, RIP-qPCR, and m6A quantification to elucidate mechanisms.
Main Results:
- METTL3 and METTL5 were found to be upregulated, while METTL4 was downregulated in CRPC.
- METTL3 knockdown significantly inhibited CRPC cell proliferation, migration, invasion, and epithelial-mesenchymal transition, and suppressed tumor growth in vivo.
- METTL3 promotes CRPC by enhancing m6A methylation and stability of AKR1C3, leading to increased AR signaling.
Conclusions:
- METTL3 functions as an epigenetic driver in CRPC by promoting AKR1C3 expression via an m6A-dependent mechanism.
- The METTL3/AKR1C3 axis represents a potential therapeutic target for treating castration-resistant prostate cancer.
Keywords:
aldo‐keto reductase family 1 member C3androgen receptor signalingcastration‐resistant prostate cancermethyltransferase‐like 3More Related Videos
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