Tumor-derived PRMT1 suppresses macrophage antitumor activity by inhibiting cGAS/STING signaling in gastric cancer cells

Q: What role does PRMT1 play in gastric cancer progression?

PRMT1 is reported to be upregulated in gastric cancer and to promote tumor progression by acting as an immunosuppressive factor.

Q: How does PRMT1 knockdown affect cGAS/STING signaling and IFN-β?

PRMT1 knockdown enhances dsDNA aggregation, activates the cGAS/STING pathway, and increases IFN-β secretion.

Q: How is macrophage polarization altered after targeting STING in the context of PRMT1 knockdown?

Targeted STING inhibition reverses the progression benefit and the macrophage polarization changes caused by PRMT1 knockdown, shifting the polarization back from the altered state.

Sep 23, 2026

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Gastric cancer (GC) is linked to epigenetic alterations that shape tumor-associated macrophages. PRMT1 is identified as an immunosuppressive factor upregulated in GC and promoting tumor progression. PRMT1 knockdown activates cGAS/STING signaling through enhanced dsDNA aggregation, increasing IFN-β secretion and remodeling macrophage polarization toward more M1-like and less M2-like phenotypes in vivo and in vitro.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

PRMT1 in cancer biology and immunotherapy

Tumor microenvironment and macrophage polarization

Study rationale

[www.nature.com/cddis](www.nature.com/cddis) ARTICLE OPEN Tumor-derived PRMT1 suppresses macrophage antitumor activity by inhibiting cGAS/STING signaling in gastric cancer cells Hui Wang 1,2,3,6, He Nie2,3,6, Xiaoyi Zhao2,3,6, Ke Chen2,3, Chen Peng1, Xuemei Zhang1, Huiweng Guo 1, Yijia Chen1, Xiaojing Yang4,5, Dong Wang4,5, Yongbing Yang4,5 ✉, Qibin He 1 ✉ and Qiang Zhan 2,3 ✉ © The Author(s) 2025 | | | | | --- | --- | --- | | | Gastric cancer (GC) is a common and aggressive malignancy worldwide. Increasing evidence has shown that epigenetic changes are closely related to the development of cancer and tumor-associated macrophages. Here, we report that PRMT1 is a key immunosuppressive factor in GC. PRMT1 is upregulated in GC and promotes tumor progression. PRMT1 knockdown in GC leads to the activation of the cGAS/STING pathway through the enhancement of dsDNA aggregation, which subsequently increases IFN-β secretion. Notably, after PRMT1 knockdown, M1-like tumor-associated macrophage (TAM) inﬁltration increased, whereas M2-like TAM inﬁltration decreased in vivo and in vitro. After the targeted inhibition of STING by siRNA or H151, the improvement in the progression of GC caused by PRMT1 knockdown decreased, and the changes in macrophage polarization were reversed. Furthermore, we found that PRMT1 knockdown in GC affects the STAT pathway in TAMs, inducing changes in their polarization and promoting GC apoptosis by enhancing IFN-β secretion through the cGAS/STING pathway. In summary, our ﬁndings revealed that PRMT1 knockdown inhibits the cGAS/STING | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | pathway in GC, which produces type I IFNs to promote the polarization of M1-like macrophages in the tumor microenvironment. | | | | | Cell Death and Disease (2025)16:649; [https://doi.org/10.1038/s41419-025-07960-y](https://doi.org/10.1038/s41419-025-07960-y) | | | | | | INTRODUCTION Gastric cancer (GC) is an aggressive and recalcitrant malignant tumor with the ﬁfth highest incidence and the second highest mortality rate worldwide, seriously endangering public health [1] . Although the standard treatment for GC has signiﬁcantly improved, it is still limited to surgical resection, chemotherapy and radiotherapy [2] . The survival rate of patients with GC has not signiﬁcantly improved, with the 5 year overall survival rate remaining <30%[3] . Over the past few years, immune checkpoint inhibitors have demonstrated promising advantages in the treatment of various cancers, although their effectiveness has been disappointing in GC patients [4] . Thus, ﬁnding an effective therapeutic target to increase the sensitivity of GC to immune checkpoint inhibitors is essential. PRMT1, a main member of the protein arginine methyltransferases (PRMTs), plays a role in a variety of cellular processes, including transcriptional regulation, RNA processing, DNA damage repair, and signal transduction [5, 6] . Noteworthily, the overexpression of PRMT1 has been associated with the progression of various cancers through its transcriptional effects on carcinogenic factors [7, 8] . Previous studies have reported a strong correlation between PRMTs and the anticancer immune response, suggesting the key role of PRMTs in modulating the effectiveness of immunotherapy [9] . For example, alterations in PRMT1 function can modulate B-cell proliferation, differentiation, and survival in humoral immunity [10] . Moreover, PRMT1 is highly expressed in T cells and increases the expression of IL-10 and IL-6 to inhibit tumor growth in hepatocellular carcinoma [11] . Therefore, manipulating PRMT1 may be a viable strategy for modulating the tumor microenvironment. However, the speciﬁc role of PRMT1 in the GC tumor immune microenvironment (TME) has not been reported. The TME is important for the development and progression of GC, consisting of a complex community composed of cancer cells, immune cel

FAQs

What role does PRMT1 play in gastric cancer progression?

PRMT1 is reported to be upregulated in gastric cancer and to promote tumor progression by acting as an immunosuppressive factor.

How does PRMT1 knockdown affect cGAS/STING signaling and IFN-β?

PRMT1 knockdown enhances dsDNA aggregation, activates the cGAS/STING pathway, and increases IFN-β secretion.

How is macrophage polarization altered after targeting STING in the context of PRMT1 knockdown?

Targeted STING inhibition reverses the progression benefit and the macrophage polarization changes caused by PRMT1 knockdown, shifting the polarization back from the altered state.

Sep 23, 2026

Uploaded by McGucket