Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and in vitro Studies

Abstract

Background: Shenling Baizhu Powder (SBP), a famous Traditional Chinese Medicine (TCM) formulation, has been widely used in the adjuvant treatment of cancers, including breast cancer. This study aims to identify potential new targets for breast cancer treatment based on the network pharmacology of SBP. Methods: By analyzing the relationship between herbs and target proteins, potential targets of multiple herbs in SBP were identified by network pharmacology analysis. Besides, by comparing the data of breast cancer tissue with normal tissue, upregulated genes in two breast cancer expression profiles were found. Thereafter, the expression level and prognosis of activator of heat shock protein 90 (HSP90) ATPase activity 1 (AHSA1) were further analyzed in breast cancer by bioinformatics analysis, and the network module of AHSA1 binding protein was constructed. Furthermore, the effect of knocking down AHSA1 on the proliferation, migration, and invasion of breast cancer cells was verified by MTT, clone formation assay, and transwell assay. Results: Vascular endothelial growth factor A (VEGFA), intercellular adhesion molecule 1 (ICAM1), chemokine (C-X-C motif) ligand 8 (CXCL8), AHSA1, and serpin family E member 1 (SERPINE1) were associated with multiple herbs in SBP. AHSA1 was remarkably upregulated in breast cancer tissues and positively correlated with poor overall survival and disease metastasis- free survival. Furthermore, knockdown of AHSA1 significantly inhibited the migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells but had no obvious effect on proliferation. In addition, among the proteins that bind to AHSAl, the network composed of proteasome, chaperonin, and heat shock proteins is closely connected, and these proteins are associated with poor prognosis in a variety of cancers. Conclusion: AHSA1 is positively correlated with breast cancer progression and might act as a novel therapeutic target for breast cancer.