Characteristics of Aurora Kinase A-Mediated Tumor Microenvironment in Colorectal Cancer and Mining of Active Compounds From Chinese Herbs

LI Mengyao, HUA Dongming, WANG Zhiyan, LIU Zhiyi, GONG Hangjun, SUN Yunchuan, HU Xueqing, WANG Yan

Abstract

To investigate the effects of Aurora kinase A (AURKA) on the tumor microenvironment of colorectal cancer (CRC) and to predict the active compounds in Chinese herbs that can target AURKA.

Methods 

Based on the transcriptomic data and clinical information from 380 CRC tissues and 51 paracancerous tissues in The Cancer Genome Atlas (TCGA) database, the infiltration of different cells in the tumor tissues was analyzed using xCell and the binding of active compounds of Chinese herbs with AURKA was predicted through molecular docking.

Results 

 The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues (P < 0.05), and CRC patients with high AURKA expression had shorter overall survival. Compared with the AURKA low-expression group, the abundance of macrophages, monocytes, and effector memory CD4+ and CD8+ T cells was significantly downregulated in the AURKA high-expression group (P < 0.05). In addition, the cytotoxicity of T cells was significantly reduced (P < 0.05). Further analysis revealed that AURKA expression was positively correlated with the abundance of myeloid-derived suppressor cells (MDSCs) and the expression levels of their chemokines CXCL2 and CXCL5 (P < 0.05). Genes that were differentially expressed between the AURKA high- and low-expression groups were mainly enriched in monocyte migration, chemokine-induced cellular responses, and other related processes. Chinese herbal compounds, including hesperidin, aristololactam A Ⅱa, anacardic acid, coumestrol, and 17β -estradiol, all showed binding energies to AURKA lower than −1.2 kcal/mol, indicating a certain level of binding stability. Among these Chinese herbal compounds, 17β-estradiol exhibited the best binding stability to AURKA-3UOL.

Conclusion 

The high expression of AURKA in CRC tissues suggests a poor clinical prognosis. AURKA can promote the development of a suppressive immune microenvironment in CRC, and 17β-estradiol, an active compound from Chinese herbs, is a potential therapeutic agent targeting AURKA.

 

Keywords: Colorectal cancer, Aurora kinase A, Immune microenvironment, Traditional Chinese medicine, Active compound

 

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References


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