As speculated, PTEN knockdown aggravated the molecular, cellular, and pathological alterations in BPH rats’ prostate and amplified TGF-β-induced changes in BPH-1 cells; more importantly, PTEN knockdown partially abolished the improving effects of METTL3 knockdown both in vivo and in vitro, suggesting that METTL3 exerts its functions in BPH through mediating the m6A modification of PTEN. This evidence concerns the gene PTEN and benign prostatic hyperplasia.