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Cancer Cell International
Published in: Cancer Cell International 1/2021

Open Access 01-12-2021 | Gastrointestinal Stromal Tumor | Primary research

Aurora kinase A (AURKA) promotes the progression and imatinib resistance of advanced gastrointestinal stromal tumors

Authors: Xiaobin Cheng, Jinhai Wang, Sen Lu, Weina Fan, Weilin Wang

Published in: Cancer Cell International | Issue 1/2021

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Abstract

Background

Gastrointestinal stromal tumor (GIST) is a common tumor that originates from the alimentary system mesenchyme. Compared to typical gastrointestinal carcinomas, GISTs exhibit unique malignant behaviors. Bioinformatic tools and subsequent experiments were applied to investigate novel targets involved in GIST progression and imatinib resistance.

Methods

Differences in gene expression profiles between advanced and nonadvanced GISTs were comprehensively analyzed based on the Gene Expression Omnibus (GEO) dataset GSE136755. A protein–protein interaction (PPI) network was constructed to identify the potential target gene. Gene set enrichment analysis (GSEA) was used to elucidate relevant biological events related to the target gene based on the GSE47911 dataset. Subsequently, immunohistochemistry and Kaplan–Meier analysis were performed to validate the prognostic value of the target gene in GISTs. Overexpression of the target gene was conducted to analyze its function in the proliferation, apoptosis, and imatinib resistance of GIST/T1 cells.

Results

In the current study, a total of 606 differentially expressed genes (DEGs) were screened based on the GSE136755 dataset, and the upregulated DEGs in advanced GISTs were mainly involved in cell division through functional annotations. The intersecting hub gene, Aurora kinase A (AURKA), was identified by degree and bottleneck algorithms. GSEA revealed that AURKA was involved in cell cycle-related biological processes. Analysis of the Oncomine and GEPIA databases revealed a pattern of elevated AURKA expression in most human malignances. Clinical assays demonstrated that AURKA could be an independent prognostic factor for GISTs. Additionally, overexpression of AURKA was experimentally demonstrated to promote cell proliferation, inhibit cell apoptosis, and enhance imatinib resistance in GIST/T1 cells.

Conclusions

These findings indicated that overexpression of AURKA promoted GIST progression and enhanced imatinib resistance, implying that AURKA is a potential therapeutic target for GISTs.
Appendix
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Metadata
Title
Aurora kinase A (AURKA) promotes the progression and imatinib resistance of advanced gastrointestinal stromal tumors
Authors
Xiaobin Cheng
Jinhai Wang
Sen Lu
Weina Fan
Weilin Wang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-02111-7

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