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Research Paper|Volume 11, Issue 24|pp 12754—12772

Expression profile-based screening for critical genes reveals S100A4, ACKR3 and CDH1 in docetaxel-resistant prostate cancer cells

Sha Zhu1,4, Zhixue Min2, Xianli Qiao4, Shengxian Chen4, Jian Yang3, Xiao Zhang1, Xigang Liu1, Weijie Ran1, Renguang Lv1, Ying Lin1, Jin Wang1
  • 1Key laboratory of Tumor Immunology, Center of Infection and Immunization, Department of Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, P. R. China
  • 2The Third People’s Hospital of Zhengzhou, Zhengzhou 450000, P.R. China
  • 3School of Medicine, Shanghai Jiao Tong University, Shanghai 20040, P.R. China
  • 4Collaborative Innovation Center of Cancer Chemoprevention, School of Physics and Engineering, Zhengzhou University, Zhengzhou 450001, P. R. China
Received: June 28, 2019Accepted: December 2, 2019Published: December 29, 2019
https://doi.org/10.18632/aging.102600

Copyright © 2019 Zhu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Docetaxel is a first-line anticancer drug widely used in the treatment of advanced prostate cancer. However, its therapeutic efficacy is limited by its side effects and the development of chemoresistance by the tumor. Using a gene differential expression microarray, we identified 449 genes differentially expressed in docetaxel-resistant DU145 and PC3 cell lines as compared to docetaxel-sensitive controls. Moreover, western blotting and immunohistochemistry revealed altered expression of S100A4, ACKR3 and CDH1in clinical tumor samples. Cytoscape software was used to investigate the relationship between critical proteins and their signaling transduction networks. Functional and pathway enrichment analyses revealed that these signaling pathways were closely related to cellular proliferation, cell adhesion, cell migration and metastasis. In addition, ACKR3 knockout using the crispr/cas9 method andS100A4knockdownusing targeted shRNA exerted additive effects suppressing cancer cell proliferation and migration. This exploratory analysis provides information about potential candidate genes. It also provides new insight into the molecular mechanism underlying docetaxel-resistance in androgen-independent prostate cancer and highlights potential targets to improve therapeutic outcomes.