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Updated: Aug 23, 2025

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer
Daisy B Haigh1,2, Corinne L Woodcock1,2, Jennifer Lothion-Roy1,2
1Biodiscovery Institute, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Abstract:
Prostate cancer (PCa) is a leading cause of cancer-related deaths and is driven by aberrant androgen receptor (AR) signalling. For this reason, androgen deprivation therapies (ADTs) that suppress androgen-induced PCa progression either by preventing androgen biosynthesis or via AR signalling inhibition (ARSi) are common treatments. The N6-methyladenosine (m6A) RNA modification is involved in regulating mRNA expression, translation, and alternative splicing, and through these mechanisms has been implicated in cancer development and progression. RNA-m6A is dynamically regulated by the METTL3 RNA methyltransferase complex and the FTO and ALKBH5 demethylases. While there is evidence supporting a role for aberrant METTL3 in many cancer types, including localised PCa, the wider contribution of METTL3, and by inference m6A, in androgen signalling in PCa remains poorly understood. Therefore, the aim of this study was to investigate the expression of METTL3 in PCa patients and study the clinical and functional relevance of METTL3 in PCa. It was found that METTL3 is aberrantly expressed in PCa patient samples and that siRNA-mediated METTL3 knockdown or METTL3-pharmacological inhibition significantly alters the basal and androgen-regulated transcriptome in PCa, which supports targeting m6A as a novel approach to modulate androgen signalling in PCa.
Insights
METTL3, a key regulator of N6-methyladenosine (m6A) RNA modification, is aberrantly expressed in prostate cancer (PCa). Targeting m6A offers a novel strategy to modulate androgen signaling in PCa.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Prostate cancer (PCa) is a major cause of cancer mortality, driven by androgen receptor (AR) signaling.
- Androgen deprivation therapies (ADTs) are standard treatments, targeting androgen biosynthesis or AR signaling inhibition (ARSi).
- N6-methyladenosine (m6A) RNA modification, regulated by METTL3, influences gene expression and is implicated in cancer progression.
Purpose of the Study:
- To investigate METTL3 expression in PCa patients.
- To determine the clinical and functional relevance of METTL3 in PCa.
- To explore the role of METTL3 and m6A in androgen signaling within PCa.
Main Methods:
- Analysis of METTL3 expression in PCa patient samples.
- siRNA-mediated knockdown of METTL3.
- Pharmacological inhibition of METTL3.
- Transcriptome analysis to assess changes in gene expression.
Main Results:
- METTL3 is aberrantly expressed in PCa patient samples.
- METTL3 knockdown or inhibition significantly alters the basal and androgen-regulated transcriptome in PCa.
- These findings suggest a critical role for METTL3 in regulating androgen signaling pathways.
Conclusions:
- METTL3 plays a significant role in prostate cancer progression and androgen signaling.
- Targeting m6A RNA modification represents a promising novel therapeutic strategy for PCa.
- Further research into METTL3 inhibition could lead to new treatments for PCa.
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