ABSTRACT
OBJECTIVES: The purpose of this study is to decipher the role of Cullin family genes in colorectal cancer (CRC), drawing insights from comprehensive analyses encompassing multiple databases and experimental validations. METHODS: UALCAN, GEPIA2, Human Protein Atlas (HPA), KM plotter, cBioPortal, TISIDB, DAVID, colon cancer cell lines culturing, gene knockdown, CCK8 assay, colony formation, and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) assays. RESULTS: Initial scrutiny of The Cancer Genome Atlas (TCGA) CRC datasets through the UALCAN and GEPIA databases unveiled significant alterations in Cullin family gene expressions. Elevations in CUL1, CUL2, CUL4A, CUL4B, CUL5, CUL7, and CUL9 were observed in CRC tissues compared to normal counterparts, while CUL3 demonstrated down-regulation consistently across datasets. Further exploration revealed notable correlations between Cullin gene expressions and various clinical parameters of CRC patients, substantiating the potential diagnostic and prognostic utility of these genes. Protein expression analyses conducted via the HPA corroborated the transcriptomic findings, indicating high levels of Cullin proteins in CRC tissues. Prognostic assessments identified CUL7 and CUL9 as significant predictors of poor survival outcomes in CRC patients, emphasizing their clinical relevance. Genetic alterations within the Cullin family genes were elucidated through the cBioPortal database, shedding light on the mutation landscape and prevalence of missense mutations in CRC. Immune subtype and tumor immune microenvironment analyses underscored the intricate interplay between Cullin family genes and immune processes in CRC. Experimental validation in CRC cell lines demonstrated the functional significance of CUL7 and CUL9 in promoting CRC growth, further solidifying their roles as potential therapeutic targets. CONCLUSION: Overall, these multifaceted analyses elucidated the intricate involvement of Cullin family genes in CRC pathogenesis and provided valuable insights for future diagnostic and therapeutic endeavors in CRC management.
