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极光激酶A(AURKA)作为一种潜在的预后生物标志物,可调节鼻咽癌中的自噬和免疫浸润。

AURKA, as a potential prognostic biomarker, regulates autophagy and immune infiltration in nasopharyngeal carcinoma.

作者信息

Jiang Danxian, Chen Huikuan, Cao Jinxin, Chen Yonghua, Huang Jing, Weng Yijie

机构信息

Department of Head and Neck Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.

Department of Otorhinolaryngology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.

出版信息

Immunobiology. 2023 Mar;228(2):152314. doi: 10.1016/j.imbio.2022.152314. Epub 2022 Dec 19.

Abstract

BACKGROUND

Dysfunction of Aurora A (AURKA) plays crucial role in tumorigenesis and development of many types of cancer. However, the role of AURKA in nasopharyngeal carcinoma (NPC) has not been investigated yet.

MATERIALS AND METHODS

Two independent NPC cohorts (GSE61218 and GSE102349) were enrolled from public database to investigate the expression level of AURKA between NPC and nasopharyngitis samples, the association of AURKA expression level with prognosis in NPC, and the potential mechanism of AURKA in NPC by using bioinformatics analyses. The expression level of AURKA protein in 62 paired NPC and nasopharyngitis tissues was evaluated by immunohistochemistry (IHC). Two NPC cell lines (SUNE-1 and CNE-2) were enrolled and the expression levels of AURKA in the NPC cells were inhibited by RNA interference. The expression levels of mRNAs were tested by qPCR and western-blotting. CCK-8 assay was applied to measure the cell growth. Cell migration was measured by using wound healing assays.

RESULTS

AURKA was highly expressed in NPC samples compared to nasopharyngitis samples in GSE61218, which was confirmed by IHC. High expression of AURKA was associated with worse prognosis in GSE102349. Notably, silencing of AURKA was associated with significantly decreased cell growth and migration in NPC. Moreover, we found that the differentially expressed genes between high and low AURKA expression groups in GSE102349 were majorly enriched in both autophagy-related and immune-related pathways. Additionally, the expression level of AURKA was associated with the expression levels of autophagy-related genes and the infiltration of immune cells.

CONCLUSION

AURKA overexpressed in NPC, which was associated with poor prognosis. Silencing of AURKA inhibited the proliferation and migration of NPC cells. Besides, AURKA might participate in the regulation of both autophagy and immunity in NPC.

摘要

背景

极光激酶A(AURKA)功能失调在多种癌症的发生和发展中起关键作用。然而,AURKA在鼻咽癌(NPC)中的作用尚未得到研究。

材料与方法

从公共数据库中纳入两个独立的NPC队列(GSE61218和GSE102349),通过生物信息学分析研究NPC与鼻咽炎样本之间AURKA的表达水平、AURKA表达水平与NPC预后的关联以及AURKA在NPC中的潜在机制。通过免疫组织化学(IHC)评估62对NPC和鼻咽炎组织中AURKA蛋白的表达水平。纳入两个NPC细胞系(SUNE-1和CNE-2),通过RNA干扰抑制NPC细胞中AURKA的表达水平。通过qPCR和蛋白质印迹法检测mRNA的表达水平。应用CCK-8法检测细胞生长情况。采用伤口愈合试验检测细胞迁移情况。

结果

在GSE61218中,与鼻咽炎样本相比,NPC样本中AURKA高表达,这通过IHC得到证实。在GSE102349中,AURKA高表达与较差的预后相关。值得注意的是,沉默AURKA与NPC细胞生长和迁移显著降低相关。此外,我们发现GSE102349中AURKA高表达组和低表达组之间的差异表达基因主要富集在自噬相关和免疫相关途径中。此外,AURKA的表达水平与自噬相关基因的表达水平和免疫细胞浸润相关。

结论

AURKA在NPC中过表达,这与不良预后相关。沉默AURKA可抑制NPC细胞的增殖和迁移。此外,AURKA可能参与NPC中自噬和免疫的调节。

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