Dataset Information

IL-8-mediated overexpression of ZNF274 promotes the proliferation and migration of colorectal cancer cells through the transactivation of MRPL40

ABSTRACT:

Background

Colorectal cancer (CRC) is one of the most prevalent malignant tumors with high morbidity and mortality rates worldwide. ZNF274, a member of the zinc-finger-protein family of transcription factors, is critical in chromosomal remodelling and tumorigenesis. However, the role of ZNF274 in CRC and the underlying molecular mechanisms remain unclear.

Methods

Immunohistochemical analysis was performed to quantify the expression of ZNF274 in human CRC tissues. The Kaplan‒Meier method was used to analyse the relationship between ZNF274 expression and CRC prognosis. The correlation between ZNF274 expression and clinical features was analyzed using Cox regression analysis. Cell proliferation and migration were evaluated by CCK-8, colony formation, and Transwell assays. The limma R package was used to analyse IL-8-related differentially expressed genes in the GSE30364 dataset. The DAVID method was used to screen significantly enriched pathways. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were performed to determine the transcriptional regulation of MRPL40 by ZNF274.

Results

ZNF274 was overexpressed in CRC tissues and indicated poor prognosis. High ZNF274 expression was linked to larger tumor size, invasion, lymph node metastasis, and AJCC stage. Ectopic expression promoted CRC cell proliferation and migration. Mechanistically, MRPL40 was identified as the direct target gene that transactivates the expression of ZNF274. Moreover, IL-8 upregulated ZNF274 expression in a dose-dependent manner. Downregulation of either ZNF274 or MRPL40 expression abrogated the effect of IL-8 on promoting the proliferation and migration of CRC.

Conclusion

This study revealed an oncogenic role of ZNF274 and the mechanism by which ZNF274 participated in IL-8-induced promotion of CRC progression. These findings demonstrate that ZNF274 could be used as a prognostic factor and potential therapeutic target for CRC treatment. Graphical abstract Image 1 Highlights • IL-8 activates ZNF274 and mitochondrial gene expression• High ZNF274 expression indicates poor prognosis in CRC patients• Ectopic expression of ZNF274 promotes CRC cell proliferation and migration• ZNF274 transcriptionally activates MRPL40• ZNF274 and MRPL40 are essential for IL8-mediated CRC progression

SUBMITTER: Du F

PROVIDER: S-EPMC10450991 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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