Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and holds the second highest mortality rate among cancers, as reported by the International Agency for Research on Cancer in 2022. Our laboratory has developed a comprehensive functional genomics database from 104 Taiwanese CRC patients using next-generation sequencing (NGS) technology. This database has facilitated the identification of a 13-gene signature that is predictive for both diagnostic and prognostic applications in CRC. Notably, one gene, DLG5, exhibited a positive correlation with tumor progression and distant metastasis. Elevated levels of DLG5 were associated with reduced survival and increased recurrence rates, suggesting its potential role as an oncogene and a biomarker for CRC prognosis and diagnosis. DLG5 is a member of the MAGUK family, which is crucial for maintaining cell polarity through the formation of the SCRIB-LGL-DLG complex. However, the role of DLG5 in CRC remains unexplored.

Employed siRNA to downregulate DLG5 expression in HCT116 CRC cells. To preform proliferative test, we conduct colony formation assay. To preform cell migratory test, we conduct migration and invasion assay. Further investigations were conducted using NGS, quantitative PCR, and Western blot analyses to delve into the potential regulatory mechanisms.

Downregulate DLG5 reduced the proliferative and migratory abilities, which supports its oncogenic function. Preliminary analyses suggest that DLG5 may influence several pathways including epithelial-mesenchymal transition (EMT), extracellular matrix organization, and immune-related pathways. These findings indicate a multifaceted role of DLG5 in CRC pathogenesis. Further experimental studies are necessary to elucidate the detailed mechanisms by which DLG5 contributes to CRC progression and to assess its viability as a therapeutic target. This study underscores the potential of DLG5 as an oncogenic factor in CRC and as a candidate for clinical biomarker development. By investigating its regulatory pathways, we aim to highlight new therapeutic avenues for CRC treatment.

1. Through the integration of functional genomic data and clinical analysis from a Taiwan-based CRC cohort, our study identifies DLG5 as a significant biomarker for poor prognosis and distant metastasis. 2. Inhibition of DLG5 expression significantly reduces the proliferative and migratory abilities of CRC cells. 3. Transcriptome profiling reveals that DLG5 may participate in several pathways, including EMT, extracellular matrix organization, and immune-related pathways. 4. Validation of DLG5's potential downstream targets was performed through Western blotting and quantitative PCR. 5. Further experimental studies are necessary to elucidate the detailed mechanisms by which DLG5 contributes to CRC progression and to assess its viability as a therapeutic target.