睡眠不足诱导的致癌途径是通过神经元特异性白细胞介素-1受体附属蛋白(AcPb)介导的。

IF 8.8 2区 医学 Q1 IMMUNOLOGY
Yool Lee , Erika L. English , Catherine M. Schwartzmann , Yiyong Liu , James M. Krueger
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引用次数: 0

摘要

白细胞介素-1β(IL1)是一种多效细胞因子,参与睡眠调节、肿瘤的发生和免疫反应。IL1 受体适配蛋白,包括 IL1 受体附属蛋白(AcP)及其神经元特异异构体 AcPb,是 IL1 信号传导所必需的。AcPb 异构体是 AcP 转录本交替剪接的结果。我们之前使用 AcPb 空值(AcPb-/-)小鼠进行的研究揭示了它参与睡眠调节和神经元/胶质细胞网络特性的特点。在这里,我们采用 RNA 测序方法研究了急性睡眠中断(SD)对野生型(WT)和 AcPb-/- 小鼠脑癌相关通路的影响。在WT小鼠中,SD增加了AcPb mRNA水平,但没有增加AcP mRNA水平,这证实了之前在大鼠中进行的类似研究。转录组和通路富集分析表明,SD 后 WT 小鼠的癌症、免疫和病毒性疾病相关通路发生了显著变化,而 AcPb-/- 小鼠的这些变化有所减弱,其中包括与癌症进展和转移相关的多个 Src 磷酸化信号依赖基因的上调。我们在癌症基因组图谱计划(TCGA)数据库中对 RNAseq 研究结果进行了分析,结果显示,与正常组织相比,包括脑肿瘤在内的各种肿瘤中与睡眠和癌症相关的基因(如 IL-17B、IL-17RA、LCN2)都出现了上调。通过TCGA分析确定的睡眠相关因素对患者的预后和生存有重大影响,尤其是在低级别胶质瘤(LGG)和多形性胶质母细胞瘤(GBM)患者中。总之,我们的研究结果表明,SD通过AcPb调控通路促进了有利于肿瘤的环境。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sleep loss-induced oncogenic pathways are mediated via the neuron-specific interleukin-1 receptor accessory protein (AcPb)
Interleukin-1β (IL1), a pleiotropic cytokine, is involved in sleep regulation, tumor ontogeny, and immune responses. IL1 receptor adaptor proteins, including the IL1 receptor accessory protein (AcP), and its neuron-specific isoform, AcPb, are required for IL1 signaling. The AcPb isoform is resultant from alternate splicing of the AcP transcript. Our previous studies using AcPb null (AcPb-/-) mice characterized its participation in sleep regulation and emergent neuronal/glial network properties. Here, we investigated the impact of acute sleep disruption (SD) on brain cancer-related pathways in wild-type (WT) and AcPb-/- mice, employing RNA sequencing methods. In WT mice, SD increased AcPb mRNA levels, but not AcP mRNA, confirming prior similar work in rats. Transcriptome and pathway enrichment analyses demonstrated significant alterations in cancer, immune, and viral disease-related pathways in WT mice after SD, which were attenuated in AcPb-/- mice including multiple upregulated Src phosphorylation-signaling-dependent genes associated with cancer progression and metastasis. Our RNAseq findings, were analyzed within the context of The Cancer Genome Atlas Program (TCGA) data base; revealing an upregulation of sleep- and cancer-linked genes (e.g., IL-17B, IL-17RA, LCN2) across various tumors, including brain tumors, compared to normal tissues. Sleep-linked factors, identified through TCGA analyses, significantly impact patient prognosis and survival, particularly in low-grade glioma (LGG) and glioblastoma multiforme (GBM) patients. Overall, our findings suggest that SD promotes a pro-tumor environment through AcPb-modulated pathways.
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来源期刊
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
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