JMJD3 modulates benign prostatic hyperplasia through epigenetic regulation of TGF-β1.

Benign prostatic hyperplasia (BPH) is a common chronic disease among elderly men, and its etiology remains unclear. This study aimed to investigate the expression, biological function, and underlying mechanism of JMJD3 in BPH. Here, we identified that JMJD3 is a crucial driver of BPH progression. In this work, both scRNA and bulk sequencing data revealed that JMJD3 is upregulated in BPH, which was further validated in prostate tissues from BPH patients. Functionally, Overexpressing JMJD3 could promote cell proliferation and cell cycles in WPMY-1 and RWPE-1 cells, respectively. Whereas, blocking JMJD3 with GSK-J4 or siRNA may induce cell apoptosis, and inhibit cell proliferation and cell cycles in BPH-1 cells. Furthermore, inhibition of JMJD3 with GSK-J4 could alleviate both testosterone and lipopolysaccharide (LPS) induced BPH in vivo. Mechanistically, JMJD3 demethylates H3K27me3 at the promoter of TGF-β1 to promote its expression and then promotes disease progression in BPH. In summary, our findings illustrate JMJD3's contribution to BPH progression and offer a potential JMJD3-targeted therapy for BPH. Our findings illustrated JMJD3's contribution to BPH progression, and GSK-J4 offers a potential JMJD3-targeted therapy for BPH.