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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Quercetin Suppresses Uterine Leiomyoma Progression by Modulating METTL3-Mediated MAPK Signaling

by
Wenting Luo
1,
Xuan Yang
1,2,
Yu Liu
1,
Tiantian Qiu
1,3,
Hui Ren
1,
Jiheng Zuo
1,
Zongshun Chen
1,
Shuoshuo Shi
1 and
Donghua Li
1,*
1
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
2
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
3
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(10), 4586; https://doi.org/10.3390/ijms27104586
Submission received: 6 April 2026 / Revised: 9 May 2026 / Accepted: 18 May 2026 / Published: 20 May 2026
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Uterine leiomyoma (UL) is characterized by excessive proliferation, extracellular matrix accumulation, and inflammatory activation, yet its upstream regulatory mechanisms remain incompletely defined. Here, we investigated the role of METTL3-associated signaling in mediating the anti-leiomyoma effects of quercetin. Quercetin significantly inhibited proliferation and induced apoptosis in UL cells, accompanied by suppression of inflammatory cytokine production. Transcriptomic profiling revealed that METTL3 silencing was associated with enrichment of MAPK and inflammation-related pathways. Mechanistically, quercetin downregulated METTL3 expression and suppressed phosphorylation of MEK, ERK, JNK, and p38, whereas METTL3 overexpression partially reversed these effects, supporting a functional role of METTL3 in mediating MAPK pathway activation. Consistently, METTL3 knockdown recapitulated the anti-proliferative, pro-apoptotic, and anti-inflammatory effects of quercetin. In a hormone-induced UL rat model, quercetin attenuated uterine enlargement, fibrosis, and proliferative activity, accompanied by decreased METTL3 expression and MAPK activation. Collectively, these findings demonstrate that quercetin suppresses UL progression, at least in part, through modulation of METTL3-mediated MAPK signaling, highlighting METTL3 as a critical regulatory node and a potential therapeutic target in UL.
Keywords: quercetin; uterine leiomyoma; METTL3; MAPK signaling; proliferation; apoptosis; inflammation quercetin; uterine leiomyoma; METTL3; MAPK signaling; proliferation; apoptosis; inflammation
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MDPI and ACS Style

Luo, W.; Yang, X.; Liu, Y.; Qiu, T.; Ren, H.; Zuo, J.; Chen, Z.; Shi, S.; Li, D. Quercetin Suppresses Uterine Leiomyoma Progression by Modulating METTL3-Mediated MAPK Signaling. Int. J. Mol. Sci. 2026, 27, 4586. https://doi.org/10.3390/ijms27104586

AMA Style

Luo W, Yang X, Liu Y, Qiu T, Ren H, Zuo J, Chen Z, Shi S, Li D. Quercetin Suppresses Uterine Leiomyoma Progression by Modulating METTL3-Mediated MAPK Signaling. International Journal of Molecular Sciences. 2026; 27(10):4586. https://doi.org/10.3390/ijms27104586

Chicago/Turabian Style

Luo, Wenting, Xuan Yang, Yu Liu, Tiantian Qiu, Hui Ren, Jiheng Zuo, Zongshun Chen, Shuoshuo Shi, and Donghua Li. 2026. "Quercetin Suppresses Uterine Leiomyoma Progression by Modulating METTL3-Mediated MAPK Signaling" International Journal of Molecular Sciences 27, no. 10: 4586. https://doi.org/10.3390/ijms27104586

APA Style

Luo, W., Yang, X., Liu, Y., Qiu, T., Ren, H., Zuo, J., Chen, Z., Shi, S., & Li, D. (2026). Quercetin Suppresses Uterine Leiomyoma Progression by Modulating METTL3-Mediated MAPK Signaling. International Journal of Molecular Sciences, 27(10), 4586. https://doi.org/10.3390/ijms27104586

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