Low-dose hexavalent chromium(VI) exposure promotes prostate cancer cell proliferation by activating MAGEB2-AR signal pathway.

Abstract

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with several malignancies, such as lung cancer, but little information was available about the effects of its low-dose environmental exposure in prostate cancer. Our previous study has shown that low-dose Cr(VI) exposure could promote prostate cancer(PCa) cell growth in vitro and in vivo. In the present study, we furthermore found that low-dose Cr(VI) exposure could induce DNA demethylation in PCa cells. Based on our transcriptome sequencing data and DNA methylation database, we further identified MAGEB2 as a potential effector target that contributed to tumor-promoting effect of low-dose Cr(VI) exposure in PCa. In addition, we demonstrated that MAGEB2 was upregulated in PCa and its knockdown restrained PCa cell proliferation and tumor growth in vitro and in vivo. Moreover, Co-IP and point mutation experiments confirmed that MAGEB2 could bind to the NH2-terminal NTD domain of AR through the F-box in the MAGE homology domain, and then activated AR through up-regulating its downstream targets PSA and NX3.1. Together, low-dose Cr(VI) exposure can induce DNA demethylation in prostate cancer cells, and promote cell proliferation via activating MAGEB2-AR signaling pathway. Thus, inhibition of MAGEB2-AR signaling is a novel and promising strategy to reverse low-dose Cr(VI) exposure-induced prostate tumor progression, also as effective adjuvant therapy for AR signaling-dependent PCa.

• Authors: Yunkai Qie, Diansheng Zhou, Zhouliang Wu, Shenglai Liu, Chong Shen, Hailong Hu, Changwen Zhang, Yong Xu
• Journal: Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 241 Pg. 113724 (Aug 2022) ISSN: 1090-2414 [Electronic] Netherlands
• PMID: 35660381 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• AR protein, human
• Antigens, Neoplasm
• Carcinogens, Environmental
• MAGEB2 protein, human
• Neoplasm Proteins
• Receptors, Androgen
• Chromium
• chromium hexavalent ion

Topics

• Antigens, Neoplasm (genetics, metabolism)
• Carcinogens, Environmental (toxicity)
• Cell Proliferation (drug effects)
• Chromium (toxicity)
• Humans
• Male
• Neoplasm Proteins (genetics, metabolism)
• Prostatic Neoplasms (genetics, metabolism)
• Receptors, Androgen (metabolism)
• Signal Transduction (drug effects)