MYC/TXNIP轴介导肺腺癌中ncl抑制的CD8+T细胞免疫应答。

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Dan Xiao, Tanxiu Chen, Xinlin Yu, Ying Song, Yigang Liu, Wei Yan
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引用次数: 0

摘要

背景:肺腺癌是一种致命的恶性肿瘤,免疫逃避在肿瘤的发展中起着关键作用。糖代谢对T细胞功能至关重要,核仁蛋白NCL可能影响T细胞糖代谢。本研究旨在探讨NCL在肺腺癌细胞T细胞糖代谢和免疫逃避中的作用。方法:利用基因表达图谱(Gene Expression Omnibus, GEO)和癌症基因组图谱(Cancer Genome Atlas, TCGA)的单细胞RNA测序(scRNA-seq)数据,分析细胞聚类、注释和预后。体外实验通过调控CD8+ T细胞中NCL的表达来研究免疫功能和葡萄糖代谢。使用原位移植小鼠模型的体内研究监测了NCL对CD8+ T细胞糖代谢和抗肿瘤免疫功能的影响。结果:NCL与T细胞功能障碍和糖代谢有关。NCL沉默增强CD8+ T细胞的糖代谢、细胞毒性和浸润,而NCL过表达则具有相反的作用。NCL过表达减轻myc介导的TXNIP转录抑制,降低CD8+ T细胞糖代谢。在体内,NCL通过MYC/TXNIP轴抑制CD8+ T细胞糖代谢,阻碍抗肿瘤免疫功能。结论:NCL过表达抑制CD8+ T细胞糖代谢和抗肿瘤免疫功能,通过MYC/TXNIP轴促进肺腺癌进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The MYC/TXNIP axis mediates NCL-Suppressed CD8+T cell immune response in lung adenocarcinoma.

Background: Lung adenocarcinoma is a deadly malignancy with immune evasion playing a key role in tumor progression. Glucose metabolism is crucial for T cell function, and the nucleolar protein NCL may influence T cell glucose metabolism. This study aims to investigate NCL's role in T cell glucose metabolism and immune evasion by lung adenocarcinoma cells.

Methods: Utilizing single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), we analyzed cell clustering, annotation, and prognosis. In vitro experiments involved manipulating NCL expression in CD8+ T cells to study immune function and glucose metabolism. In vivo studies using an orthotopic transplant mouse model monitored NCL's impact on CD8+ T cell glucose metabolism and anti-tumor immune function.

Results: NCL was associated with T cell dysfunction and glucose metabolism. NCL silencing enhanced CD8+ T cell glucose metabolism, cytotoxicity, and infiltration, while NCL overexpression had the opposite effect. NCL overexpression relieved MYC-mediated transcriptional repression of TXNIP, reducing CD8+ T cell glucose metabolism. In vivo, NCL inhibited CD8+ T cell glucose metabolism through the MYC/TXNIP axis, hindering anti-tumor immune function.

Conclusions: NCL overexpression suppresses CD8+ T cell glucose metabolism and anti-tumor immune function, promoting lung adenocarcinoma progression via the MYC/TXNIP axis.

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来源期刊
Molecular Medicine
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.
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