ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCommunity Series in Biomarker Discovery and Therapeutic Innovations in Genito-Urinary Cancer Management Volume IIView all 9 articles
Miltirone promotes pyroptosis via increasing pyroptosis-related protein NLRP3 and AIM2 in kidney renal clear cell carcinoma
Provisionally accepted
- The Affiliated Hospital of Qingdao University, Qingdao, China
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Background: Pyroptosis, a type of programmed cell death, exert direct influence on inflammatory processes and immune response. Previous study suggests that Miltirone exhibits notable anti-tumor activities and has been shown to induce tumor cell pyroptosis. Nevertheless, the therapeutic value of Miltirone in kidney renal clear cell carcinoma (KIRC) remains under-explored. Methods and Results: Using TCGA pan-cancer data, we uncovered the widely expressed of pyroptosis-related genes (NLRP3 and AIM2). Mechanistically, the genomic amplification alteration and high CNV percentages in pan-caner induced abnormal expression. StromalScore analysis suggested that NLRP3 and AIM2 were activated by tumor immune microenvironment in KIRC. Enrichment analysis indicated that NLRP3 and AIM2 regulated inflammatory response and related to immune infiltration in KIRC. Furthermore, Kaplan-Meier curve and ROC analysis indicated that high expression of AIM2 was associated with worse prognosis of KIRC patients. MTT assays and flow cytometry revealed that Miltirone treatment induced KIRC cell pyroptosis and inhibited cell proliferation, with changes in the expression level of NLPR3, AIM2, caspase-3 and GSDMD. The enhancement of cell pyroptosis, IL-1β and IL-18 cytokines release was reversed by pretreatment of pyroptosis inhibitor VX-765. Conclusions: Our study revealed the prognostic value of NLRP3 and AIM2 in KIRC. Miltirone treatment inhibited KIRC cell proliferation and enhanced cell pyroptosis via NLRP3/AIM2/GSDMD axis. This study provides a novel molecular mechanism and potential therapeutic targets in KIRC progression.
Keywords: immune, kidney renal clear cell carcinoma, Miltirone, prognosis, pyroptosis
Received: 10 Sep 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Huang, Wang, Gao, Wang, Guo, Song, He and Cai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tao Huang
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