JQ1 Downregulates IL-20RA Expression in Triple Negative Breast Cancer Cells In Vitro and In Vivo

The dynamic crosstalk between the tumor microenvironment (TME) and triple negative breast cancer (TNBC) cells plays a critical role in tumor progression and treatment resistance. Recent studies have highlighted the involvement of IL-20 receptor subunit alpha (IL-20RA) signaling in BC, where its overexpression modulates oncogenic pathways contributing to invasion and metastasis. Epigenetic dysregulation by Bromodomain and Extra-Terminal domain (BET) proteins critically influences key oncogenic pathways and cytokine expression in TNBC. Given that the BET-inhibitor JQ1 blocks TNBC cell growth, in this study we investigated its potential regulatory effects on the IL-20RA pathway. IL-20RA was found expressed across multiple BC cell lines compared to non-tumorigenic cells, with the highest levels detected in MDA-MB-231 and MDA-MB-468 cells. In both cell lines, JQ1 treatment significantly downregulated IL-20RA expression at gene and protein levels, accompanied by a reduction in the oncogenic JAK/STAT signaling pathway, and programmed death-ligand 1 (PD-L1) expression. Parallel in vivo experiments using TNBC xenograft models confirmed these findings, showing reduced IL-20RA and PD-L1 expression alongside decreased phosphorylation of JAK and STAT3. Overall, this study uncovers a novel interplay between BET inhibition and the IL-20RA/STAT3 axis, suggesting JQ1 as a valid therapeutic option for TNBC characterized by high IL-20RA expression.