Upregulation of PSMD4 gene by hypoxia in prostate cancer cells

Abstract

Ubiquitin-proteasome pathways have a crucial role in tumor progression. PSMD4 (Rpn10, 26S proteasome non-ATPasesubunit 4), which is a subunit of the regulatory particle, is a major ubiquitin (Ub) receptor of 26S proteasome. PSMD4 overexpressionhas been observed in colon carcinoma, hepatocellular carcinoma, and breast cancer. In this work, we elucidated the effect of hypoxia onPSMD4 gene expression in prostate cancer cells (PC3). Chemically mimicked hypoxia drastically upregulated PSMD4 gene expressionat both mRNA and protein levels. Transient transfection experiments indicated that all promoter fragments were active in PC3 cells.Hypoxia increased transcriptional activity of all PSMD4 promoter constructs. EMSA analysis shows that HIF-1a transcription factorbinds to the hypoxia response element (HRE) present within the –98/+52 region of PSMD4 promoter. We also used human umbilicalvein endothelial cell (HUVEC) as a different cell model, in which increased PSMD4 expression was seen only at 24 h. The increasedexpression of the PSMD4 level in the PC3 cell line was not parallel to the expression in hypoxic HUVEC.