# The emerging role of m6A methylation in prostate-related diseases: mechanisms and clinical implications

## TL;DR

This paper reviews how m6A RNA methylation influences prostate diseases like prostatitis, BPH, and prostate cancer, and how targeting this process could lead to new diagnostics and treatments.

## Contribution

The paper systematically reviews the role of m6A methylation in prostate-related diseases and highlights its potential as a therapeutic and diagnostic target.

## Key findings

- m6A methylation regulates prostate disease progression through altered cell proliferation, inflammation, and immune responses.
- Dysregulation of m6A components like METTL3, FTO, and YTHDF1 contributes to prostatitis, BPH, and prostate cancer.
- m6A modifications influence immunosuppressive environments in prostate cancer by modulating immune checkpoints like PD-L1.

## Abstract

Prostate-related diseases, including prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa), represent significant threats to the health of the aging male population worldwide. Despite their prevalence, the pathogenesis of prostate-related diseases has not been elucidated. Recent studies have shown that N6-methyladenosine (m6A) modification is widely involved in the progression of prostate-related diseases. In this review, we summarized recent advances in understanding the core m6A regulatory machinery comprising writers such as the methyltransferase-like 3 (METTL3)-METTL14 complex, erasers including fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5), and readers, including the YTH domain-containing family proteins (YTHDFs), YTHDC proteins, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs), and heterogeneous nuclear ribonucleoproteins (HNRNPs). Specifically, we elucidated how dysregulation of these components drives disease progression via alterations in cellular proliferation, differentiation, inflammatory responses, and stem cell dynamics. Notably, m6A modifications help shape the immunosuppressive landscape in PCa by modulating immune checkpoint expression, cytokine networks, and immune cell infiltration, thereby critically influencing therapeutic responses to immunotherapy. Furthermore, this review highlights the emerging diagnostic potential and therapeutic viability of m6A-targeted strategies, offering valuable insights for future clinical translation in prostate-related diseases.

N6-methyladenosine (m6A) RNA methylation dynamically orchestrates prostate physiology and pathology through the coordinated actions of writers (e.g., METTL3, METTL14, and WTAP), erasers (FTO and ALKBH5), and readers (YTHDF1, YTHDF2, YTHDC1), which together regulate mRNA stability, splicing, translation, and decay. This epitranscriptomic machinery modulates key cellular processes, including proliferation, differentiation, inflammatory responses, and stemness, within the prostate gland, as illustrated by the central anatomical depiction of the human prostate. Dysregulation of m6A modification drives a pathological continuum: in prostatitis, aberrant m6A signaling exacerbates chronic inflammation via altered cytokine production and immune cell infiltration; in benign prostatic hyperplasia (BPH), it promotes stromal and epithelial hyperplasia by enhancing cell growth and suppressing apoptosis; and in prostate cancer (PCa), m6A imbalance fosters tumor progression through oncogene activation, tumor suppressor silencing, and the establishment of an immunosuppressive microenvironment, characterized by upregulated immune checkpoints (e.g., PD-L1) and impaired T-cell infiltration. Collectively, this visual narrative positions m6A methylation as a pivotal epigenetic switch across the spectrum of prostate-related diseases, highlighting its emerging potential as a source of diagnostic biomarkers and therapeutic targets in precision oncology.Diagram illustrating the role of m⁶A modification abnormalities in prostate conditions. VCAN, PTEN, and MYC/AR influence m⁶A modifications. Abnormalities lead to prostatitis, mediated by TNF-α and TGF-β, and influence factors like NF-κB and IL-6/IL-8. These contribute to benign prostatic hyperplasia (BPH) and prostate cancer (PCa) through tissue remodeling, EMT, AR, and local hypoxia, with pathways such as direct transformation, PIA lesion, and HGPIN formation. Arrows indicate the progression and impact on the human prostate.

N6-methyladenosine (m6A) RNA methylation dynamically orchestrates prostate physiology and pathology through the coordinated actions of writers (e.g., METTL3, METTL14, and WTAP), erasers (FTO and ALKBH5), and readers (YTHDF1, YTHDF2, YTHDC1), which together regulate mRNA stability, splicing, translation, and decay. This epitranscriptomic machinery modulates key cellular processes, including proliferation, differentiation, inflammatory responses, and stemness, within the prostate gland, as illustrated by the central anatomical depiction of the human prostate. Dysregulation of m6A modification drives a pathological continuum: in prostatitis, aberrant m6A signaling exacerbates chronic inflammation via altered cytokine production and immune cell infiltration; in benign prostatic hyperplasia (BPH), it promotes stromal and epithelial hyperplasia by enhancing cell growth and suppressing apoptosis; and in prostate cancer (PCa), m6A imbalance fosters tumor progression through oncogene activation, tumor suppressor silencing, and the establishment of an immunosuppressive microenvironment, characterized by upregulated immune checkpoints (e.g., PD-L1) and impaired T-cell infiltration. Collectively, this visual narrative positions m6A methylation as a pivotal epigenetic switch across the spectrum of prostate-related diseases, highlighting its emerging potential as a source of diagnostic biomarkers and therapeutic targets in precision oncology.