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Volume 27
Issue 12
10.3390/ijms27125233
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Communication

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

by
Valentina Maggisano
1,
Salvatore Panza
2,
Antonella Verrienti
3,
Giovanni Enrico Lombardo
4,
Stefania Catalano
5,6 and
Stefania Bulotta
1,*
1
Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
2
Department of Experimental and Clinical Medicine, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
3
Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
4
Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy
5
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (Cosenza), Italy
6
Centro Sanitario, University of Calabria, 87036 Arcavacata di Rende (Cosenza), Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(12), 5233; https://doi.org/10.3390/ijms27125233 (registering DOI)
Submission received: 29 April 2026 / Revised: 3 June 2026 / Accepted: 5 June 2026 / Published: 9 June 2026
(This article belongs to the Special Issue Cancer Drugs That Target Epigenetic Processes)
Versions Notes

Abstract

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.
Keywords: TNBC; TME; IL-20RA; BET-inhibitor; JQ1 TNBC; TME; IL-20RA; BET-inhibitor; JQ1

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MDPI and ACS Style

Maggisano, V.; Panza, S.; Verrienti, A.; Lombardo, G.E.; Catalano, S.; Bulotta, S. JQ1 Downregulates IL-20RA Expression in Triple Negative Breast Cancer Cells In Vitro and In Vivo. Int. J. Mol. Sci. 2026, 27, 5233. https://doi.org/10.3390/ijms27125233

AMA Style

Maggisano V, Panza S, Verrienti A, Lombardo GE, Catalano S, Bulotta S. JQ1 Downregulates IL-20RA Expression in Triple Negative Breast Cancer Cells In Vitro and In Vivo. International Journal of Molecular Sciences. 2026; 27(12):5233. https://doi.org/10.3390/ijms27125233

Chicago/Turabian Style

Maggisano, Valentina, Salvatore Panza, Antonella Verrienti, Giovanni Enrico Lombardo, Stefania Catalano, and Stefania Bulotta. 2026. "JQ1 Downregulates IL-20RA Expression in Triple Negative Breast Cancer Cells In Vitro and In Vivo" International Journal of Molecular Sciences 27, no. 12: 5233. https://doi.org/10.3390/ijms27125233

APA Style

Maggisano, V., Panza, S., Verrienti, A., Lombardo, G. E., Catalano, S., & Bulotta, S. (2026). JQ1 Downregulates IL-20RA Expression in Triple Negative Breast Cancer Cells In Vitro and In Vivo. International Journal of Molecular Sciences, 27(12), 5233. https://doi.org/10.3390/ijms27125233

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