PRMT6 promotes the immune evasion of gastric cancer via upregulating ANXA1

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2024-03-01 DOI:10.1615/critreveukaryotgeneexpr.2024052979

Liang Xu, Fenger Zhang, Binqi Yu, Shengnan Jia, Sunfu Fan

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Abstract

Gastric cancer is a most malignancy in digestive tract worldwide. This study aimed to investigate the roles of PRMT6 in gastric cancer. Immunohistochemistry was performed to detect PRMT6 expression in gastric tumors. RT-qPCR was used to detected mRNA levels. Protein expression was determined using western blot. Gastric cancer cells were co-cultured with CD8+ T cells. Colony formation assay was performed to detect cell proliferation. Flow cytometry was performed to determine CD8+ T cell function and tumor cell apoptosis. PRMT6 was overexpressed in gastric tumors. High level of PRMT6 predicted poor outcomes of gastric cancer patients and inhibition of CD8+ T cell infiltration. PRMT6 promoted proliferation of CD8+ T cells and enhanced its tumor killing ability. Moreover, PRMT6 upregulated ANXA1 and promoted ANXA1 protein stability. ANXA1 overexpression suppressed the proliferation of CD8+ T cells and promoted tumor cell survival. PRMT6 functions as an oncogene in gastric cancer. PRMT6-mediated protein stability inhibits the infiltration of CD8+ T cells, resulting in immune evasion of gastric cancer. The PRMT6-ANXA1 may be a promising strategy for gastric cancer.

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PRMT6 通过上调 ANXA1 促进胃癌的免疫逃避

胃癌是全球消化道中最常见的恶性肿瘤。本研究旨在探讨 PRMT6 在胃癌中的作用。免疫组化法检测胃癌中 PRMT6 的表达。采用 RT-qPCR 检测 mRNA 水平。蛋白表达用 Western 印迹法测定。胃癌细胞与 CD8+ T 细胞共同培养。进行集落形成试验检测细胞增殖。流式细胞术检测 CD8+ T 细胞功能和肿瘤细胞凋亡。PRMT6在胃肿瘤中过表达。高水平的PRMT6预示着胃癌患者的不良预后以及对CD8+ T细胞浸润的抑制。PRMT6 促进了 CD8+ T 细胞的增殖，增强了其杀伤肿瘤的能力。此外，PRMT6 上调 ANXA1 并促进 ANXA1 蛋白的稳定性。ANXA1 的过表达抑制了 CD8+ T 细胞的增殖，促进了肿瘤细胞的存活。PRMT6是胃癌的致癌基因。PRMT6 介导的蛋白稳定性抑制了 CD8+ T 细胞的浸润，从而导致胃癌的免疫逃避。PRMT6-ANXA1可能是一种治疗胃癌的有前途的策略。

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来源期刊

Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物

CiteScore

2.70

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.