Work

Exploring the regulatory mechanism of CCNA2 in colorectal cancer: Insights from multiomics and experimental analysis

Year: 2025

Type: article

Abstract: Colorectal cancer (CRC) is the third-most common cancer and the second leading of cancer-related deaths worldwide. The underlying regulatory mechanism of cyclin A2 (CCNA2) in CRC was explored through multiomics and experimental analyses, thus facilitating diagnosis, therapy, and prognosis. GSE9348 and GSE110223 were extracted from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified via GEO2R. CCNA2, a core gene for CRC, was screened out from the protein-protein interaction network constructed by differentially expressed genes. Its diagnostic, prognostic, and therapeutic value was evaluated in Gene Expression Omnibus, The Cancer Genome Atlas, Human Protein Atlas, and Drug-Gene interaction database via transcriptomics, proteomics, and pharmacogenomics. The correlation between CCNA2 and immune infiltration was determined in Tumor Immune Estimation Resource by immunomics. Transcription factor-mRNA and miRNA-mRNA networks for CCNA2 were constructed in miRnet and miRDB via transcriptomics. The role and regulatory mechanism of CCNA2 in CRC were investigated both in vitro and in vivo. CCNA2 showed excellent diagnostic, therapeutic, and prognostic value in CRC. CCNA2 was closely associated with tumor-infiltrating immunocytes, transcription factors, and miRNAs. The knockdown of CCNA2 inhibited the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), while inducing apoptosis of CRC cells. CCNA2 acted as a target of miR-548x-3p in regulating the biological behavior of CRC cells via the EMT-signaling pathway. CCNA2 is a potential biomarker for the diagnosis, treatment, and prognosis of CRC. The miR-548x-3p-CCNA2 axis plays a pivotal role in regulating the tumorigenesis of CRC through the EMT-signaling pathway.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.110216