TRIM23 promotes 5-Fluorouracil resistance in colorectal cancer by upregulating GALNT4 expression.

5-Fluorouracil (5-FU) is one of the most common chemotherapeutic agents for colorectal cancer (CRC), but its application is often limited by resistance. Tripartite motif containing 23 (TRIM23) has been reported to be dysregulated in various tumors and involved in tumor progression and chemotherapy resistance. However, its relationship with CRC 5-FU resistance and the underlying mechanism are still unclear. In this study, we found that TRIM23 was upregulated in CRC. Patients treated with 5-FU and with high TRIM23 expression had a lower disease control rate (DCR) and a poorer median progression-free survival (mPFS). In vitro, the expression of TRIM23 in CRC cells was elevated after 5-FU treatment. Compared to parental cells, TRIM23 was significantly overexpressed in 5-FU-resistant CRC cells. Mechanistically, TRIM23 mediated 5-FU resistance of CRC by upregulating the expression of N-acetylgalactosaminyltransferase-4 (GALNT4). Knocking down TRIM23 in 5-FU-resistant colon cancer cells restored the sensitivity to 5-FU, while overexpression of GALNT4 in TRIM23 knockdown cells counteracted the chemosensitization caused by TRIM23 downregulation. The TRIM23/GALNT4 axis may play a crucial role in 5-FU resistance in CRC, and targeted inhibition of this axis is expected to reverse resistance. As a potential biomarker for screening 5-FU-sensitive patients and predicting prognosis in clinical practice, TRIM23 deserves further investigation.