Elevated UBC9 expression and its oncogenic role in colorectal cancer progression and chemoresistance

Colorectal cancer (CRC) is a highly prevalent and fatal malignancy, with incidence and mortality rates rising globally. While elevated UBC9 expression has been implicated in various cancers, its specific role in CRC remains poorly understood. This study aims to investigate the expression levels, prognostic significance, and functional roles of UBC9 in CRC. We assessed the expression and prognostic value of UBC9 mRNA and protein in colorectal cancer separately using multiple databases and immunohistochemical techniques. Additionally, in vitro functional assays and in vivo zebrafish tumor models were employed to elucidate the role of UBC9 in CRC cell proliferation, migration, invasion, and chemoresistance. UBC9 expression was significantly upregulated in CRC tissues. Elevated UBC9 levels were associated with poor prognosis in chemotherapy-treated CRC patients. Gene Set Enrichment Analysis revealed that pathways related to MYC targets, DNA repair, and oxidative stress response were enriched in groups with high UBC9 expression. Immune profiling indicated reduced infiltration of CD4+ memory-activated T cells and NK cells in tumors with elevated UBC9 levels. Functional assays demonstrated that UBC9 knockdown inhibited CRC cell proliferation, migration, and invasion, and sensitized cells to oxaliplatin, which was further validated using zebrafish xenograft models. UBC9 is crucial for CRC progression, genomic instability, and chemoresistance. It represents a potential prognostic biomarker and therapeutic target, particularly for enhancing chemotherapy efficacy in CRC patients.