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IRAK家族基因的全癌综合分析确定IRAK1是低级别胶质瘤中的一种新型癌基因。

Comprehensive Pan-Cancer Analysis of IRAK Family Genes Identifies IRAK1 as a Novel Oncogene in Low-Grade Glioma.

作者信息

Li Jing, Sun Yuchen, Ma Yuan, Zhao Xu, Sun Xuanzi, Wang Yuzhu, Zhang Xiaozhi

机构信息

The First Affiliated Hospital of Xi'an Jiaotong University, Department of Radiation Oncology, Xi'an 710061, China.

出版信息

J Oncol. 2022 Feb 15;2022:6497241. doi: 10.1155/2022/6497241. eCollection 2022.

DOI:10.1155/2022/6497241
PMID:35211171
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8863493/
Abstract

BACKGROUND

The interleukin-1 receptor-associated kinases (IRAK) family genes, indispensable mediators of interleukin-1 receptor (IL1R) and Toll-like receptor (TLR)-inflammatory signaling, may be involved in the biological function of human cancers due to the crucial roles of inflammation in tumor development. Though a little research has demonstrated the function of individual IRAK family members in specific tumors, comprehensive analysis is still lacking in pan-cancer.

METHODS

We analyzed the mRNA expression landscape, mutation, and prognosis value of IRAK genes based on The Cancer Genome Atlas (TCGA), cBioPortal, GlioVis, and Rembrandt databases. The correlation between the expression of IRAK genes and tumor microenvironment (TME), Stemness score, and immune subtypes was explored. Western blot, cell proliferation, apoptosis, migration assays, and xenograft models were utilized in this study.

RESULTS

We found that the expression of IRAK genes extensively changed and was related to patient survival in pan-cancer. Besides, IRAK family genes were correlated with TME, Stemness score, and immune subtypes in most cases. Given that high expression of all IRAK family members predicted poor prognosis in low-grade glioma (LGG), the oncogenic function of the highest expressed IRAK1 in LGG has been confirmed in vitro and in vivo. IRAK1 was uncovered to inhibit cell apoptosis and augment malignancy of LGG in vitro and in vivo.

CONCLUSION

These findings revealed the potential targets of IRAK family genes in pan-cancer and provided insights for further investigation of IRAK1 as a novel oncogenic gene in LGG.

摘要

背景

白细胞介素-1受体相关激酶（IRAK）家族基因是白细胞介素-1受体（IL1R）和Toll样受体（TLR）炎症信号传导中不可或缺的介质，由于炎症在肿瘤发生发展中的关键作用，可能参与人类癌症的生物学功能。尽管已有少量研究证实了个别IRAK家族成员在特定肿瘤中的功能，但在泛癌研究中仍缺乏全面分析。

方法

我们基于癌症基因组图谱（TCGA）、cBioPortal、GlioVis和Rembrandt数据库分析了IRAK基因的mRNA表达谱、突变情况及预后价值。探讨了IRAK基因表达与肿瘤微环境（TME）、干性评分及免疫亚型之间的相关性。本研究采用了蛋白质免疫印迹法、细胞增殖、凋亡、迁移实验及异种移植模型。

结果

我们发现IRAK基因的表达在泛癌中广泛变化，且与患者生存相关。此外，在大多数情况下，IRAK家族基因与TME、干性评分及免疫亚型相关。鉴于所有IRAK家族成员的高表达预示着低级别胶质瘤（LGG）患者预后不良，我们在体外和体内证实了LGG中表达最高的IRAK1的致癌功能。研究发现，IRAK1在体外和体内均可抑制LGG细胞凋亡并增强其恶性程度。

结论

这些发现揭示了IRAK家族基因在泛癌中的潜在靶点，并为进一步研究IRAK1作为LGG中的新型致癌基因提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e45/8863493/74e2c54b3b2b/JO2022-6497241.010.jpg
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