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ARID3A 通过上调 AURKA 促进结直肠癌的发展。

ARID3A promotes the development of colorectal cancer by upregulating AURKA.

机构信息

Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Department of Pathology, Harbin Medical University, Harbin, China.

出版信息

Carcinogenesis. 2021 Apr 30;42(4):578-586. doi: 10.1093/carcin/bgaa118.

DOI:10.1093/carcin/bgaa118
PMID:33165575
Abstract

Colorectal cancer (CRC) is one of the most common malignant tumours, and its morbidity and mortality rates are relatively high. However, the aetiology and pathogenesis of CRC have not been clearly elucidated to date. AT-rich interaction domain 3A (ARID3A) is a member of the ARID3 family and a transcription factor that can bind to specific DNA sites to regulate gene expression. It was reported that ARID3A is involved in various biological processes and may be related to carcinogenesis. In this study, by assessing the mRNA level of ARID3A in TCGA database, we found that ARID3A expression increased in CRC tissues, and proposed that ARID3A could act as a tumour-promoting factor in the development of CRC. To verify this hypothesis, we used cell proliferation, migration and invasion assays to assess the effect of ARID3A on CRC cells. We revealed that ARID3A overexpression enhanced tumour cell proliferation, migration and invasion. ARID3A could target Aurora kinase A (AURKA) to facilitate the malignant phenotype of CRC cells, and patients with a higher ratio of AURKA and ARID3A had a better overall survival. Conclusively, this study showed that ARID3A targeted AURKA to facilitate the development of CRC. The ratio of ARID3A and AURKA could be used as a potential biomarker to predict prognosis, providing a new strategy for the diagnosis and prognosis of CRC.

摘要

结直肠癌(CRC)是最常见的恶性肿瘤之一,其发病率和死亡率相对较高。然而,CRC 的病因和发病机制迄今尚未阐明。富含 AT 的相互作用结构域 3A(ARID3A)是 ARID3 家族的成员,也是一种转录因子,可与特定的 DNA 位点结合,调节基因表达。有报道称,ARID3A 参与多种生物学过程,可能与肿瘤发生有关。在本研究中,通过评估 TCGA 数据库中 ARID3A 的 mRNA 水平,我们发现 ARID3A 在 CRC 组织中表达增加,并提出 ARID3A 可能在 CRC 的发展中作为一种促进肿瘤的因素。为了验证这一假设,我们使用细胞增殖、迁移和侵袭实验来评估 ARID3A 对 CRC 细胞的影响。我们揭示了 ARID3A 的过表达增强了肿瘤细胞的增殖、迁移和侵袭。ARID3A 可以靶向 Aurora 激酶 A(AURKA),促进 CRC 细胞的恶性表型,并且 AURKA 和 ARID3A 比值较高的患者总体生存率更好。综上所述,本研究表明 ARID3A 通过靶向 AURKA 促进 CRC 的发展。ARID3A 和 AURKA 的比值可以作为预测预后的潜在生物标志物,为 CRC 的诊断和预后提供了新策略。

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