In conclusion, our work promotes the potential of targeting NF-κB signaling in chemotherapy for CRC by dissecting the molecular mechanism underlines the aberrant activation of NF-κB signaling coincided with the loss of RNF138 and addresses the importance of RNF138 as a prognosis indicator for such treatments (Supplementary Fig. S11). Here, RNF138 is linked to colorectal carcinoma.