Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Jan 27, 2025; 17(1): 97148
Published online Jan 27, 2025. doi: 10.4240/wjgs.v17.i1.97148
Synergistic inhibition of colorectal cancer progression by silencing Aurora A and the targeting protein for Xklp2
Gui-Xian Sheng, Yu-Jia Zhang, Tao Shang
Gui-Xian Sheng, Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Yu-Jia Zhang, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
Tao Shang, Department of Colorectal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, Zhejiang Province, China
Co-corresponding authors: Yu-Jia Zhang and Tao Shang.
Author contributions: Sheng GX, Zhang YJ, and Shang T designed the study; Sheng GX and Shang T performed the research; Zhang YJ analyzed the data and wrote the manuscript; Shang T prepared all figures and provided guidance; All authors have reviewed and approved the final manuscript; Tao Shang and Yu-Jia Zhang contributed equally to this work and should be considered co-correspondence authors.
Institutional review board statement: The study was reviewed and approved by Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University, No. 2021-K-220-01.
Institutional animal care and use committee statement: This study did not involve any animal experiments.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: Data supporting the findings of this study are available upon request from the corresponding authors.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tao Shang, Department of Colorectal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), No. 54 Youdian Road, Shangcheng District, Hangzhou 310006, Zhejiang Province, China. shangtaomail@163.com
Received: May 24, 2024
Revised: October 10, 2024
Accepted: November 22, 2024
Published online: January 27, 2025
Processing time: 217 Days and 11.4 Hours
Abstract
BACKGROUND

Unraveling the pathogenesis of colorectal cancer (CRC) can aid in developing prevention and treatment strategies. Aurora kinase A (AURKA) is a key participant in mitotic control and interacts with its co-activator, the targeting protein for Xklp2 (TPX2) microtubule nucleation factor. AURKA is associated with poor clinical outcomes and high risks of CRC recurrence. AURKA/TPX2 co-overexpression in cancer may contribute to tumorigenesis. Despite its pivotal role in CRC development and progression, the action mechanism of AURKA remains unclear. Further research is needed to explore the complex interplay between AURKA and TPX2 and to develop effective targeted treatments for patients with CRC.

AIM

To compare effects of AURKA and TPX2 and their combined knockdown on CRC cells.

METHODS

We evaluated three CRC gene datasets about CRC (GSE32323, GSE25071, and GSE21510). Potential hub genes associated with CRC onset were identified using the Venn, search tool for the retrieval of interacting genes, and KOBAS platforms, with AURKA and TPX2 emerging as significant factors. Subsequently, cell models with knockdown of AURKA, TPX2, or both were constructed using SW480 and LOVO cells. Quantitative real-time polymerase chain reaction, western blotting, cell counting kit-8, cell cloning assays, flow cytometry, and Transwell assays were used.

RESULTS

Forty-three highly expressed genes and 39 poorly expressed genes overlapped in cancer tissues compared to controls from three datasets. In the protein-protein interaction network of highly expressed genes, AURKA was one of key genes. Its combined score with TPX2 was 0.999, and their co-expression score was 0.846. In CRC cells, knockdown of AURKA, TPX2, or both reduced cell viability and colony number, while blocking G0/G1 phase and enhancing cell apoptosis. Additionally, they were weakened cell proliferation and migration abilities. Furthermore, the expression levels of B-cell lymphoma-2-Associated X, caspase 3, and tumor protein P53, and E-cadherin increased with a decrease in B-cell lymphoma-2, N-cadherin, and vimentin proteins. These effects were amplified when both AURKA and TPX2 were concurrently downregulated.

CONCLUSION

Combined knockdown of AURKA and TPX2 was effective in suppressing the malignant phenotype in CRC. Co-inhibition of gene expression is a potential developmental direction for CRC treatment.

Keywords: Aurora kinase A; Targeting protein for Xklp2; Microtubule nucleation factor; Colorectal cancer; Proliferation; Migration; Invasion

Core Tip: In this study, we evaluated three gene datasets and identified 13 crucial genes. Results from SW480 and LOVO cells showed that Aurora kinase A (AURKA) and the targeting protein for Xklp2 (TPX2) blocked cell cycle progression and promoted cell apoptosis of colorectal cancer (CRC). Knockdown of either AURKA, TPX2, or both reduced the invasion and migration ability of CRC cells while inhibiting epithelial-mesenchymal transition. Co-knockdown of AURKA and TPX2 enhanced the inhibition of CRC cells. Combined knockdown was more effective in suppressing the malignant phenotype in CRC, providing ideas and basic data for CRC treatment.