CNOT7 Promotes Radiation Resistance in Colorectal Cancer via XRCC6-Mediated NHEJ DNA Repair Pathway

In this study, we identified CNOT7 as a key protein influencing the radiotherapy sensitivity of rectal cancer through proteomic sequencing of patient tissues. Patients with high CNOT7 expression often exhibit poorer prognoses during radiotherapy. We explored the potential mechanisms by which CNOT7 affects radiotherapy sensitivity in CRC. CNOT7 reduces polyubiquitination of K48 linked lysine 526 on XRCC6 by regulating TRIM21. This enhances DNA damage repair primarily mediated by the NHEJ pathway, thereby conferring radiotherapy resistance to colorectal cancer cells. Our study suggests that targeting CNOT7 could serve as a potential therapeutic strategy for rectal cancer patients Overall design: To investigate the function of CNOT7 in the CCR4-Not complex, we established a stable CNOT7 knockdown cell line in the CRC cell line SW480 using shRNA, and performed RNA-seq to identify downstream differentially expressed target genes.