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阿司匹林通过下调 ATAD2 和 KIF4A 的表达发挥其在食管鳞癌中的抗肿瘤作用。

Aspirin Exerts Its Antitumor Effect in Esophageal Squamous Cell Carcinoma by Downregulating the Expression of ATAD2 and KIF4A.

机构信息

Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Key Clinical Laboratory of Henan Province, Zhengzhou, Henan Province, China.

Department of Medical Laboratory, People's Hospital of Zhengzhou, Zhengzhou, Henan Province, China.

出版信息

Anal Cell Pathol (Amst). 2022 Aug 21;2022:7005328. doi: 10.1155/2022/7005328. eCollection 2022.

DOI:10.1155/2022/7005328
PMID:36046597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9420644/
Abstract

OBJECTIVE

To investigate the expression of ATPase family AAA domain-containing protein 2 (ATAD2) and kinesin family member 4A (KIF4A) in esophageal squamous cell carcinoma (ESCC) tissues and their association with clinicopathological features and to explore the role of ATAD2 in regulating KIF4A expression and biological functions in ESCC cells and the effect of aspirin on their expression.

METHODS

The mRNA and protein expression of ATAD2 and KIF4A in the tissues of patients with ESCC were measured by RT-qPCR and immunohistochemistry, and the correlation between the expression of mRNA and clinicopathological characteristics was analyzed. Western blot and RT-qPCR were used to detect the interference efficiency and KIF4A expression after si-ATAD2 transfection in EC109 and KYSE30 cells. CCK-8 and Transwell assay were performed to investigate the effects of ATAD2 and aspirin on proliferation, migration, and invasion of ESCC cells. The effect of aspirin on the expression of ATAD2 and KIF4A in ESCC cells was measured by RT-qPCR and Western blot.

RESULTS

The expression of ATAD2 and KIF4A was upregulated in ESCC tissues, and both were correlated with the differentiation grades and lymph node metastasis. Knockdown of ATAD2 in ESCC cells significantly inhibited cell proliferation, migration, and invasion. Compared to the negative control group, the proliferation, migration, and invasion ability of ESCC cells in the aspirin-treated groups were decreased, and the expression of ATAD2 and KIF4A in ESCC cells was decreased after treating with aspirin for 48 h.

CONCLUSION

The expression levels of ATAD2 and KIF4A are elevated in ESCC. ATAD2 promotes proliferation, migration, and invasion of ESCC cells by regulating KIF4A. Aspirin can inhibit the malignant behavior of ESCC cells by downregulating ATAD2 and KIF4A.

摘要

目的

研究三磷酸腺苷酶家族 AAA 结构域包含蛋白 2(ATAD2)和驱动蛋白家族成员 4A(KIF4A)在食管鳞状细胞癌(ESCC)组织中的表达及其与临床病理特征的关系,并探讨 ATAD2 调节 ESCC 细胞中 KIF4A 表达和生物学功能的作用以及阿司匹林对其表达的影响。

方法

采用 RT-qPCR 和免疫组织化学法检测 ESCC 患者组织中 ATAD2 和 KIF4A 的 mRNA 和蛋白表达情况,分析其与 mRNA 表达的相关性。采用 Western blot 和 RT-qPCR 检测 EC109 和 KYSE30 细胞中 si-ATAD2 转染后的干扰效率和 KIF4A 表达。CCK-8 和 Transwell 实验研究 ATAD2 和阿司匹林对 ESCC 细胞增殖、迁移和侵袭的影响。采用 RT-qPCR 和 Western blot 检测阿司匹林对 ESCC 细胞中 ATAD2 和 KIF4A 表达的影响。

结果

ATAD2 和 KIF4A 在 ESCC 组织中表达上调,且均与分化程度和淋巴结转移相关。在 ESCC 细胞中敲低 ATAD2 显著抑制细胞增殖、迁移和侵袭。与阴性对照组相比,阿司匹林处理组 ESCC 细胞的增殖、迁移和侵袭能力下降,阿司匹林处理 48 小时后 ESCC 细胞中 ATAD2 和 KIF4A 的表达下降。

结论

ATAD2 和 KIF4A 的表达水平在 ESCC 中升高。ATAD2 通过调节 KIF4A 促进 ESCC 细胞的增殖、迁移和侵袭。阿司匹林通过下调 ATAD2 和 KIF4A 抑制 ESCC 细胞的恶性行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1d8/9420644/43c628255577/ACP2022-7005328.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1d8/9420644/43c628255577/ACP2022-7005328.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1d8/9420644/43c628255577/ACP2022-7005328.003.jpg

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