Expression of senescence-related CD161 promotes extranodal NK/T cell lymphoma by affecting T cell phenotype and cell cycle.

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Medicine Pub Date : 2024-11-23 DOI:10.1186/s10020-024-00969-7

Chengxun Jin, Xin Li, Chaohe Zhang

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Abstract

Purpose: The intention of this work is to probe the role of senescence-related gene CD161 in extranodal NK/T cell lymphoma (ENKTL).

Methods: This study used H₂O₂ to establish three distinct in vitro oxidative stress aging models (NKL, SNT-8, and YT). Western blotting was employed to assess the levels of two iconic aging proteins, MMP1 and P53, and flow cytometry was utilized to investigate cell cycle and the expressions of CD4, CD8, and CD161. Cell viability was evaluated via the CCK-8 assay. The transcriptome analysis assessed the differential gene expression between the control and aging group of NKL. In vivo, we established a BALB/c mice aging tumor model. After 15 days, the mice were euthanized to harvest tumors. ELISA was employed to measure aging indicators in the mouse tissues. Flow cytometry was utilized to assess the levels of CD4, CD8, and CD161 in tumor samples. Hematoxylin-eosin (HE) staining was performed to evaluate the structure and cellular morphology of the tumor tissue.

Results: In the NKL, SNT-8 and YT aging models, the levels of MMP1 and P53 proteins were significantly increased. Flow cytometry results indicated that all three cell types exhibited marked arrest in the G1 phase. Compared with the control group, the expressions of CD4 and CD161 in the aging group were significantly increased, while the expression of CD8 was decreased. Transcriptome analysis revealed 2,843 differentially expressed genes (DEGs) between the control and aging groups, with 2,060 up-regulated and 783 down-regulated genes identified. Following CD161 knockdown, cell viability of three cell types in the aging group was significantly reduced compared to the control group. The G1 phase of the cells was significantly interrupted. The expressions of CD4 and CD161 were significantly increased, and the expression of CD8 was decreased. However, in the aging + si-CD161 group, a partial alleviation of oxidative stress was observed with a reduction in CD161 expression levels. Animal experiments demonstrated that knockout of CD161 can inhibit tumor progression and partially mitigate oxidative stress.

Conclusions: CD161 may inhibit ENKTL tumor development by regulating cell cycle and T-cell phenotype.

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衰老相关 CD161 的表达会影响 T 细胞表型和细胞周期，从而促进结节外 NK/T 细胞淋巴瘤的发生。

目的：本研究旨在探讨衰老相关基因 CD161 在结外 NK/T 细胞淋巴瘤（ENKTL）中的作用：本研究使用 H2O2 建立了三种不同的体外氧化应激衰老模型（NKL、SNT-8 和 YT）。采用 Western 印迹法评估两种标志性衰老蛋白 MMP1 和 P53 的水平，并利用流式细胞术研究细胞周期以及 CD4、CD8 和 CD161 的表达。细胞活力通过 CCK-8 检测法进行评估。转录组分析评估了对照组和衰老组 NKL 基因表达的差异。在体内，我们建立了一个 BALB/c 小鼠衰老肿瘤模型。15 天后，小鼠被安乐死以收获肿瘤。采用酶联免疫吸附法测定小鼠组织中的衰老指标。流式细胞术用于评估肿瘤样本中 CD4、CD8 和 CD161 的水平。对肿瘤组织的结构和细胞形态进行苏木精-伊红（HE）染色：结果：在NKL、SNT-8和YT衰老模型中，MMP1和P53蛋白水平明显升高。流式细胞术结果表明，这三种类型的细胞都明显停滞在 G1 期。与对照组相比，老化组 CD4 和 CD161 的表达量明显增加，而 CD8 的表达量减少。转录组分析显示，对照组和衰老组之间存在2843个差异表达基因（DEGs），其中上调基因2060个，下调基因783个。与对照组相比，CD161敲除后，衰老组三种细胞类型的细胞活力明显降低。细胞的 G1 期明显中断。CD4 和 CD161 的表达明显增加，CD8 的表达减少。然而，在衰老 + si-CD161 组中，随着 CD161 表达水平的降低，氧化应激也得到了部分缓解。动物实验表明，敲除 CD161 可抑制肿瘤进展并部分缓解氧化应激：CD161可通过调节细胞周期和T细胞表型抑制ENKTL肿瘤的发展。

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

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.