STEAP4 knockdown inhibits the proliferation of prostate cancer cells by activating the cGMP-PKG pathway under lipopolysaccharide-induced inflammatory microenvironment.

Abstract

Six-transmembrane epithelial antigen of prostate 4 (STEAP4) is involved in the development of human cancers. However, the role of STEAP4 in prostate cancer remains largely unknown. The purpose of this research is to explore the role and action mechanism of STEAP4 in prostate cancer development under lipopolysaccharide (LPS)-induced inflammatory microenvironment. STEAP4 expression was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN and Cancer Cell Line Encyclopedia (CCLE), and its prognostic value was analyzed by LinkedOmics. STEAP4-correlated genes were analyzed by LinkedOmics and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. STEAP4 level was detected by Western blotting or qRT-PCR. Proliferation was investigated by CCK-8 and EdU staining. Inflammatory cytokine levels were detected by ELISA. The cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway was detected by ELISA and Western blotting. STEAP4 level was increased in prostate cancer tissues, and high expression of STEAP4 was associated with the poor overall survival. LPS promoted cell viability and STEAP4 expression. STEAP4 knockdown attenuated LPS-induced inflammation in prostate cancer cells. STEAP4 downregulation mitigated LPS-induced tumorigenesis by decreasing cell proliferation. STEAP4 silencing reversed LPS-induced inactivation of the cGMP-PKG pathway. Inhibition of the cGMP-PKG pathway using inhibitor KT5823 relieved STEAP4 silencing-mediated suppression of cell proliferation and inflammation in LPS-stimulated cells. In conclusion, STEAP4 silencing inhibits LPS-induced proliferation of prostate cancer cells by activating the cGMP-PKG pathway.

• Authors: Weiwei Li, Xiurong Yin, Yani Yan, Cong Liu, Gang Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 101 Issue Pt B Pg. 108311 (Dec 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 34768126 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Lipopolysaccharides
• Membrane Proteins
• Oxidoreductases
• STEAP4 protein, human
• Cyclic GMP-Dependent Protein Kinases
• Cyclic GMP

Topics

• Animals
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclic GMP (metabolism)
• Cyclic GMP-Dependent Protein Kinases (antagonists & inhibitors, genetics, metabolism)
• Down-Regulation (drug effects)
• Humans
• Lipopolysaccharides (pharmacology)
• Male
• Membrane Proteins (metabolism)
• Oxidoreductases (genetics, metabolism)
• Prostate (metabolism)
• Prostatic Neoplasms
• Signal Transduction (drug effects)
• Tumor Microenvironment (drug effects)