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生物信息学和实验验证 AURKA/TPX2 轴作为食管鳞癌潜在靶点的研究。

Bioinformatics and experimental validation of an AURKA/TPX2 axis as a potential target in esophageal squamous cell carcinoma.

机构信息

Zhang Zhongjing School of Chinese Medicine, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China.

Oncology Department, Nanyang First People's Hospital, Nanyang, Henan 473004, P.R. China.

出版信息

Oncol Rep. 2023 Jun;49(6). doi: 10.3892/or.2023.8553. Epub 2023 Apr 21.

DOI:10.3892/or.2023.8553
PMID:37083097
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10170493/
Abstract

Aurora kinase A (AURKA), a serine/threonine kinase that regulates mitotic processes, has garnered significant interest given its association with the development of several types of cancer. In the present study, it was shown that AURKA expression was significantly upregulated in esophageal squamous cell carcinoma (ESCC) and could serve as a diagnostic and prognostic indicator based on data obtained from The Cancer Genome Atlas (TCGA) and immunohistochemical analysis. In addition, AURKA was functionally associated with ESCC cell proliferation and colony formation and knockdown of AURKA inhibited ESCC tumor growth . Both bioinformatics analysis and pull‑down assays demonstrated that TPX2 interacted with AURKA, and their expression was correlated. AURKA cooperated with TPX2 to regulate ESCC progression via the PI3K/Akt pathway. Furthermore, AURKA or TPX2 expression levels were negatively associated with the infiltration of cytotoxic cells, CD8 T cells and mast cells, but positively associated with Th2 cells. The present study provided a relatively comprehensive understanding of the oncogenic roles of AURKA in ESCC based on data obtained from TCGA combined with experimental analysis.

摘要

极光激酶 A（AURKA）是一种丝氨酸/苏氨酸激酶，可调节有丝分裂过程，由于其与多种类型癌症的发生有关，因此受到了广泛关注。本研究表明，AURKA 在食管鳞状细胞癌（ESCC）中的表达显著上调，根据从癌症基因组图谱（TCGA）和免疫组织化学分析获得的数据，它可以作为诊断和预后指标。此外，AURKA 与 ESCC 细胞增殖和集落形成具有功能相关性，并且 AURKA 的敲低抑制了 ESCC 肿瘤的生长。生物信息学分析和下拉实验均表明，TPX2 与 AURKA 相互作用，且它们的表达呈相关性。AURKA 与 TPX2 合作通过 PI3K/Akt 通路调节 ESCC 进展。此外，AURKA 或 TPX2 的表达水平与细胞毒性细胞、CD8 T 细胞和肥大细胞的浸润呈负相关，与 Th2 细胞呈正相关。本研究基于 TCGA 数据结合实验分析，对 AURKA 在 ESCC 中的致癌作用有了较为全面的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/b2686803b98a/or-49-06-08553-g07.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/6e686e547674/or-49-06-08553-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/b2686803b98a/or-49-06-08553-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/3546e5564996/or-49-06-08553-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/b07e3b32d867/or-49-06-08553-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/dd2ee833dcaf/or-49-06-08553-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/3d78f6a98e9c/or-49-06-08553-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/ee75e04d1320/or-49-06-08553-g04.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10170493/6e686e547674/or-49-06-08553-g06.jpg
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