Faculty Collaboration Database

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1. Cell Signal 2024 Jul;119:111180

Date

04/21/2024

Pubmed ID

38642782

DOI

10.1016/j.cellsig.2024.111180

Scopus ID

2-s2.0-85190884720 (requires institutional sign-in at Scopus site)

Abstract

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

Author List

Geng T, Sun Q, He J, Chen Y, Cheng W, Shen J, Liu B, Zhang M, Wang S, Asan K, Song M, Gao Q, Song Y, Liu R, Liu X, Ding Y, Jing A, Ye X, Ren H, Zeng K, Zhou Y, Zhang B, Ma S, Liu W, Liu S, Ji J

Author

Wei Liu PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Cell Proliferation
DNA-Binding Proteins
Early Growth Response Protein 1
Female
Gene Expression Regulation, Neoplastic
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Inflammation
Mice
Mice, Nude
Ovarian Neoplasms
Signal Transduction
Trans-Activators
Transcription Factors
Transcriptional Activation