Silencing Uracil-DNA glycosylase inhibits colorectal cancer progression

Dysregulation of repair pathways, specifically the base excision repair (BER) axis, is frequently observed in cancer. This dysfunction is associated with accelerated tumor growth and reduced patient survival, suggesting that BER components may serve as potential targets for cancer therapy. This study focused on the expression of Uracil-DNA glycosylase (UNG), a key enzyme in BER, in colorectal tumor tissues and adjacent normal tissues. We systematically explored the clinical significance, biological functions, and molecular mechanisms of UNG in colorectal cancer (CRC). Our findings revealed that UNG was significantly upregulated in CRC, and its higher expression correlated with poorer patient outcomes. Functional assays demonstrated that silencing UNG inhibited cell proliferation, reduced migration and invasion capabilities, and induced apoptosis along with S/G2 phase cell cycle arrest. Mechanistically, UNG appears to interact with the AMPK, AKT/mTOR, and ERK signaling pathways. These results suggested that UNG exhibited oncogenic potential in CRC by regulating malignant behaviors and oncogenic signaling cascades, positioned it as a potential prognostic biomarker and therapeutic target for CRC treatment.