Although p21 is mainly regulated by p53 at the transcription level, multiple transcription factors (BRCA1, Smad3, AP4 and c-myc) have also been reported to control the transcriptional activation or repression of p21 [39–41].In our study, TRIB2 could negatively regulate p21 promoter activities and expression, and inhibit cellular senescence in CRC cells. Here, SMAD3 is linked to colorectal carcinoma.