Cellular signalling, 2024-07, Vol.119, p.111180-111180, Article 111180
2024
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1
- Ist Teil von
- Cellular signalling, 2024-07, Vol.119, p.111180-111180, Article 111180
- Ort / Verlag
- England: Elsevier Inc
- Erscheinungsjahr
- 2024
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. •CXXC5 is highly expressed in ovarian cancer and is associated with poor prognosis.•Deletion of CXXC5 inhibits ovarian cancer cell proliferation and affects inflammatory signaling pathways•The expression of CXXC5 is regulated by oxygen concentration and is the direct target of HIF1A.•ZNF143 and EGR1 are downstream transcription factors of CXXC5, which affect cell proliferation in ovarian cancer.•CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0898-6568eISSN: 1873-3913DOI: 10.1016/j.cellsig.2024.111180Titel-ID: cdi_proquest_miscellaneous_3043069196
- Format
- –
- Schlagworte
- Animals, Cell Line, Tumor, Cell Proliferation - genetics, CXXC5, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Early Growth Response Protein 1 - genetics, Early Growth Response Protein 1 - metabolism, ERG1, Female, Gene Expression Regulation, Neoplastic, Humans, Hypoxia-Inducible Factor 1, alpha Subunit - genetics, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Inflammation - genetics, Inflammation - metabolism, Inflammation - pathology, Mice, Mice, Nude, Ovarian cancer, Ovarian Neoplasms - genetics, Ovarian Neoplasms - metabolism, Ovarian Neoplasms - pathology, Signal Transduction, Trans-Activators - metabolism, Transcription factor, Transcription Factors - genetics, Transcription Factors - metabolism, Transcriptional Activation, ZNF143