METTL3 promotes prostatic hyperplasia by regulating PTEN expression in an m⁶A-YTHDF2-dependent manner

Area of Science:

• Urology
• Molecular Biology
• Epigenetics

Background:

• Benign prostatic hyperplasia (BPH) is characterized by uncontrolled epithelial cell proliferation and epithelial-mesenchymal transition (EMT).
• N6-methyladenosine (m⁶A) RNA modification influences key cellular processes like proliferation and apoptosis, suggesting a role in BPH pathogenesis.

Purpose of the Study:

• To investigate the role of methyltransferase-like 3 (METTL3) and m⁶A modification in benign prostatic hyperplasia (BPH).
• To elucidate the underlying molecular mechanisms involving the METTL3/YTHDF2/PTEN axis in BPH development.

Main Methods:

• Analysis of METTL3 expression in BPH samples.
• In vivo studies using a BPH rat model with METTL3 knockdown.
• In vitro experiments using BPH-1 cells treated with TGF-β and subjected to METTL3 or PTEN knockdown.
• Assessment of cell proliferation, apoptosis, EMT markers, and m⁶A levels.

Main Results:

• METTL3 was aberrantly upregulated in BPH samples.
• METTL3 knockdown in rats and BPH-1 cells reduced prostatic enlargement, inhibited proliferation and EMT, and promoted apoptosis.
• METTL3 knockdown decreased m⁶A levels and PTEN expression via YTHDF2.
• PTEN knockdown exacerbated BPH alterations and diminished the therapeutic effects of METTL3 knockdown.

Conclusions:

• Elevated m⁶A modification, driven by the METTL3/YTHDF2/PTEN axis, contributes to BPH pathogenesis.
• This pathway disrupts the balance of epithelial cell proliferation and apoptosis, promotes EMT, and accelerates BPH development.
• Targeting the METTL3/YTHDF2/PTEN axis may offer a therapeutic strategy for BPH.