DNMT1-mediated LAMA2 inhibition induces M2 macrophage polarization during prostate cancer progression

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-10-01 DOI:10.1016/j.tice.2025.103173

Ruiqian Li , Chen Hu , Fengming Ran , Yu Bai , Hongyi Wu , Wenjun Peng , Yixuan He , Qilin Wang , Jun Li

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引用次数: 0

Abstract

Background

Prostate cancer (PCa) presents a significant risk to the health of men, and its metastatic spread greatly affects patient survival rates and quality of life. This research investigated the role of DNA methyltransferase 1 (DNMT1) in the progression of PCa.

Methods

By performing bioinformatics analysis and in vivo and in vitro experiments, we investigated the expression levels of DNMT1 and LAMA2 in PCa. Additionally, we evaluated how they influence the proliferation and tumor microenvironment (TME) of PCa cells.

Results

DNMT1 was upregulated in PCa, whereas LAMA2 was downregulated. DNMT1 inhibited the expression of LAMA2 by promoting methylation of the LAMA2 promoter, thereby activating the PI3K/AKT signaling pathway, promoting the proliferation of PCa cells, and inducing M2 polarization of macrophages in the TME. Furthermore, DNMT1 promoted the release of the cytokines CCL5, VEGF, MMP9, and PTX3 by PC-3 cells and affected the TME.

Conclusion

This research highlights the crucial function of DNMT1 in the progression of PCa, providing new strategies for the treatment of PCa, particularly therapeutic strategies that focus on DNA methylation and tumor-associated macrophages.

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前列腺癌进展过程中dnmt1介导的LAMA2抑制诱导M2巨噬细胞极化

前列腺癌（PCa）对男性健康构成重大威胁，其转移性扩散极大地影响了患者的生存率和生活质量。本研究探讨DNA甲基转移酶1 （DNMT1）在前列腺癌进展中的作用。方法通过生物信息学分析和体内外实验，研究DNMT1和LAMA2在PCa中的表达水平。此外，我们评估了它们如何影响前列腺癌细胞的增殖和肿瘤微环境（TME）。结果PCa中dnmt1表达上调，LAMA2表达下调。DNMT1通过促进LAMA2启动子甲基化抑制LAMA2的表达，从而激活PI3K/AKT信号通路，促进PCa细胞的增殖，诱导巨噬细胞在TME中M2极化。DNMT1促进PC-3细胞释放CCL5、VEGF、MMP9、PTX3等细胞因子，影响TME。结论本研究强调了DNMT1在前列腺癌进展中的重要功能，为前列腺癌的治疗提供了新的策略，特别是针对DNA甲基化和肿瘤相关巨噬细胞的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.