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Identification and Validation of Aurora Kinase A (AURKA) Involved in the Progression and Imatinib Resistance of Advanced Gastrointestinal Stromal Tumors
Xiaobin Cheng
Zhejiang University
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Gastrointestinal stromal tumor (GIST) is a common tumor originating from mesenchyme in the alimentary system. GISTs exhibit unique malignant behavior compared to typical carcinomas. Here, we explored genes that drive the progression and imatinib resistance of GISTs by bioinformatic tools and experiments.
Methods: We analyzed gene expression profiles of GISTs and identified a key gene, AURKA, which regulated the progression of GISTs. We further determined the clinical significance of AURKA by immunohistochemical (IHC) staining assays and survival analysis. A series of in vitro experiments were performed to investigate in detail the effect of AURKA on the aggressiveness and imatinib resistance of GIST cells.
Results: Our results showed that AURKA was higher in advanced GIST tissues than in non-advanced GIST tissues. AURKA mainly involved in cell cycle related biological processes as revealed by GSEA. AURKA was positively related with GIST progression and could be an independent prognostic marker of GISTs. It was also found to exhibit consistent expression patterns in several human malignancies. Additionally, AURKA influenced gene mutations associated with imatinib resistance. Overexpression of AURKA in GIST cells promoted cell proliferation and apoptosis, even after administration of imatinib. But imatinib significantly inhibited the effects of AURKA overexpression on the migration of GIST cells.
Conclusions: Bioinformatics analyses and subsequent experiments identified AURKA as a key gene in GIST progression. AURKA showed a contribution to imatinib resistance and could be a candidate therapeutic target for GISTs.
Keywords
AURKA, Progression, Imatinib resistance, Gastrointestinal stromal tumors
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Research
Identification and Validation of Aurora Kinase A (AURKA) Involved in the Progression and Imatinib Resistance of Advanced Gastrointestinal Stromal Tumors
Xiaobin Cheng
Zhejiang University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 23 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Gastrointestinal stromal tumor (GIST) is a common tumor originating from mesenchyme in the alimentary system. GISTs exhibit unique malignant behavior compared to typical carcinomas. Here, we explored genes that drive the progression and imatinib resistance of GISTs by bioinformatic tools and experiments.
Methods: We analyzed gene expression profiles of GISTs and identified a key gene, AURKA, which regulated the progression of GISTs. We further determined the clinical significance of AURKA by immunohistochemical (IHC) staining assays and survival analysis. A series of in vitro experiments were performed to investigate in detail the effect of AURKA on the aggressiveness and imatinib resistance of GIST cells.
Results: Our results showed that AURKA was higher in advanced GIST tissues than in non-advanced GIST tissues. AURKA mainly involved in cell cycle related biological processes as revealed by GSEA. AURKA was positively related with GIST progression and could be an independent prognostic marker of GISTs. It was also found to exhibit consistent expression patterns in several human malignancies. Additionally, AURKA influenced gene mutations associated with imatinib resistance. Overexpression of AURKA in GIST cells promoted cell proliferation and apoptosis, even after administration of imatinib. But imatinib significantly inhibited the effects of AURKA overexpression on the migration of GIST cells.
Conclusions: Bioinformatics analyses and subsequent experiments identified AURKA as a key gene in GIST progression. AURKA showed a contribution to imatinib resistance and could be a candidate therapeutic target for GISTs.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7