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NEK2 promotes esophageal squamous cell carcinoma cell proliferation, migration and invasion through the Wnt/β-catenin signaling pathway
Discover Oncology Pub Date : 2023-05-26 , DOI: 10.1007/s12672-023-00692-5
Dong Guo , Weinan Yao , Xingyu Du , Jing Dong , Xueyuan Zhang , Wenbin Shen , Shuchai Zhu

Objectives

The NEK2 (never in mitosis gene A-related kinase 2), a serine/threonine kinase involved in chromosome instability and tumorigenesis. Hence, this study aimed to explore the molecular function of NEK2 in esophageal squamous cell carcinoma (ESCC).

Methods

By available transcriptome datasets (GSE53625 cohort, GSE38129 cohort, and GSE21293 cohort), we analyzed the differentially expressed genes in invading and non-invading ESCC. Subsequently, we evaluated the association between NEK2 expression level and clinical outcomes through Kaplan–Meier analysis method. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) analyses were performed to determine the expression levels of NEK2 mRNA and protein, respectively. We knocked down the NEK2 expression in ESCC cells (ECA109 and TE1), and evaluated the NEK2 biology function associated with ESCC cell proliferation, migration, invasion, and colony formation abilities. Finally, the downstream pathway of NEK2 was analyzed through Gene Set Enrichment Analysis (GSEA) and validated the regulatory mechanism of NEK2 on the potential pathway through WB.

Results

We found that NEK2 was highly expressed in ESCC cells compared with human esophageal epithelial cells (HEEC) (P < 0.0001), and high NEK2 expression was remarkably associated with poor survival (P = 0.019). Knockdown of NEK2 showed the significant inhibitory effect for tumorigenesis, and suppressed the ESCC cells proliferation, migration, invasion, and formation of colonies abilities. Additionally, GSEA revealed that Wnt/β-catenin pathway was a downstream pathway of NEK2. WB results further validated the regulatory mechanism of NEK2 for Wnt/β-catenin signaling.

Conclusions

Our results indicated that NEK2 promotes ESCC cell proliferation, migration and invasion by activating the Wnt/β-catenin pathway. NEK2 could be a promising target for ESCC.



中文翻译:

NEK2通过Wnt/β-catenin信号通路促进食管鳞癌细胞增殖、迁移和侵袭

目标

NEK2(从不在有丝分裂基因 A 相关激酶 2 中),一种参与染色体不稳定性和肿瘤发生的丝氨酸/苏氨酸激酶。因此,本研究旨在探讨NEK2在食管鳞状细胞癌(ESCC)中的分子功能。

方法

通过可用的转录组数据集(GSE53625 队列、GSE38129 队列和 GSE21293 队列),我们分析了入侵和非入侵 ESCC 中差异表达的基因。随后,我们通过 Kaplan-Meier 分析方法评估了 NEK2 表达水平与临床结果之间的关联。进行定量实时聚合酶链反应 (qRT-PCR) 和蛋白质印迹 (WB) 分析以确定 NEK2 mRNA 和蛋白质的表达水平,分别。我们敲低了 ESCC 细胞(ECA109 和 TE1)中的 NEK2 表达,并评估了与 ESCC 细胞增殖、迁移、侵袭和集落形成能力相关的 NEK2 生物学功能。最后,

结果

我们发现,与人食管上皮细胞 (HEEC) 相比,NEK2 在 ESCC 细胞中高表达 (P < 0.0001),并且 NEK2 高表达与低存活率显着相关 (P = 0.019)。敲低NEK2显示出显着的肿瘤发生抑制作用,并抑制了ESCC细胞的增殖、迁移、侵袭和集落形成能力。此外,GSEA 揭示 Wnt/β-catenin 通路是 NEK2 的下游通路。WB结果进一步验证了NEK2对Wnt/β-catenin信号通路的调控机制。

结论

我们的结果表明,NEK2 通过激活 Wnt/β-catenin 通路促进 ESCC 细胞增殖、迁移和侵袭。NEK2 可能是 ESCC 的一个有前途的目标。

更新日期:2023-05-26
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