MicroRNA-mediated crosstalk between Wnt/β-catenin signaling and the NLRP3 inflammasome in breast cancer: mechanistic evidence and therapeutic implications
Abstract
Breast cancer progression is shaped by the interaction of oncogenic signaling with chronic inflammation. Two pathways implicated in this process are NLRP3 inflammasome activation, which drives maturation of IL-1β and IL-18 and thereby reshapes the tumor microenvironment, and canonical Wnt/β-catenin signaling, which promotes proliferation, epithelial–mesenchymal transition, and stem-like properties. In this narrative review, we examine the evidence that microRNAs (miRNAs) may couple these pathways, and grade that evidence by directness and biological context. Oncogenic miRNAs including miR-21, miR-155, miR-301a, and miR-374a have been reported to enhance β-catenin signaling through suppression of PTEN and WIF1 while concurrently promoting inflammasome priming via NF-κB, whereas miR-223-3p, miR-296-5p, and miR-590-5p have been described as attenuating both. For most, however, direct experimental validation exists for only one arm of the proposed circuit, and no study has demonstrated coordinate regulation of both pathways by a single miRNA within the same breast cancer cellular context at physiological expression levels. The mechanistic anchor of the proposed module, the association of β-catenin with NLRP3 that enhances NLRP3–ASC assembly, was characterised in macrophage systems and not in breast tumour cells. We therefore distinguish evidence obtained in triple-negative breast cancer from that extrapolated from other malignancies and non-cancer inflammatory models, and note the context-dependent effects of NLRP3 signaling and pyroptosis. Therapeutic and biomarker strategies are discussed as hypotheses: no agent targeting this axis has been evaluated clinically in breast cancer. Validation in defined tumour and immune compartments, patient-derived models, and clinical cohorts is required before firm conclusions can be drawn.
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BibTeX
@article{bharti2026micrornamediated,
title = {{MicroRNA-mediated crosstalk between Wnt/β-catenin signaling and the NLRP3 inflammasome in breast cancer: mechanistic evidence and therapeutic implications}},
author = {Muskan Bharti and Shalini Mishra and Seema Khanna and Jyotsna Kailashiya and Surendra Pratap Mishra},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1956766},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1956766},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - MicroRNA-mediated crosstalk between Wnt/β-catenin signaling and the NLRP3 inflammasome in breast cancer: mechanistic evidence and therapeutic implications
AU - Muskan Bharti
AU - Shalini Mishra
AU - Seema Khanna
AU - Jyotsna Kailashiya
AU - Surendra Pratap Mishra
PY - 2026
DA - 2026/11/04
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1956766
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1956766
AB - Breast cancer progression is shaped by the interaction of oncogenic signaling with chronic inflammation. Two pathways implicated in this process are NLRP3 inflammasome activation, which drives maturation of IL-1β and IL-18 and thereby reshapes the tumor microenvironment, and canonical Wnt/β-catenin signaling, which promotes proliferation, epithelial–mesenchymal transition, and stem-like properties. In this narrative review, we examine the evidence that microRNAs (miRNAs) may couple these pathways, and grade that evidence by directness and biological context. Oncogenic miRNAs including miR-21, miR-155, miR-301a, and miR-374a have been reported to enhance β-catenin signaling through suppression of PTEN and WIF1 while concurrently promoting inflammasome priming via NF-κB, whereas miR-223-3p, miR-296-5p, and miR-590-5p have been described as attenuating both. For most, however, direct experimental validation exists for only one arm of the proposed circuit, and no study has demonstrated coordinate regulation of both pathways by a single miRNA within the same breast cancer cellular context at physiological expression levels. The mechanistic anchor of the proposed module, the association of β-catenin with NLRP3 that enhances NLRP3–ASC assembly, was characterised in macrophage systems and not in breast tumour cells. We therefore distinguish evidence obtained in triple-negative breast cancer from that extrapolated from other malignancies and non-cancer inflammatory models, and note the context-dependent effects of NLRP3 signaling and pyroptosis. Therapeutic and biomarker strategies are discussed as hypotheses: no agent targeting this axis has been evaluated clinically in breast cancer. Validation in defined tumour and immune compartments, patient-derived models, and clinical cohorts is required before firm conclusions can be drawn.
SN - 2234-943X
ER -