ZIC2 drives colorectal cancer progression by regulating QPRT-mediated cell migration

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Colorectal cancer (CRC) presents a significant mortality challenge.
• The precise role and clinical significance of Zinc finger protein 2 (ZIC2) in CRC remain largely undetermined.
• ZIC2 exhibits a complex, dual role in various cancer types.

Purpose of the Study:

• To elucidate the expression patterns and clinical significance of ZIC2 in colorectal cancer.
• To investigate the molecular mechanisms underlying ZIC2's function in CRC.
• To evaluate ZIC2 as a potential prognostic biomarker for CRC.

Main Methods:

• Analysis of TCGA and GEO datasets for ZIC2 expression and clinical correlation.
• Utilized bulk, single-cell, and spatial transcriptomic analyses.
• Weighted gene co-expression network analysis (WGCNA) to identify interacting genes, including quinolinate phosphoribosyltransferase (QPRT).
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
• Functional assays, including cell scratch assays, to validate ZIC2's role in cell migration and proliferation.

Main Results:

• ZIC2 expression is significantly upregulated in CRC tissues compared to normal tissues, associated with poorer patient prognosis.
• High ZIC2 expression correlates positively with tumor mutational burden (TMB) and microsatellite instability (MSI).
• ZIC2 promotes CRC cell migration and proliferation, partly through the upregulation of QPRT, a mechanism partially reversible by QPRT inhibition.

Conclusions:

• ZIC2 demonstrates potential as a prognostic and predictive biomarker across various cancers, including CRC.
• ZIC2 may drive colorectal cancer progression by enhancing QPRT expression and activity.
• Targeting the ZIC2-QPRT axis could offer therapeutic strategies for CRC.