STAT3 and cancer: As the decrease in STAT3 protein expression could be accounted for the decreased protein translation and increased protein degradation (or both), and the degradation of STAT3 protein is proven to be dependent on the ubiquitin-proteasome pathway 18, 19, and the clinical success of bortezomib 59 that targets ubiquitin-proteasome pathway-mediated protein degradation in cancer cells, illustrates the importance of ubiquitin-mediated signaling in cancer; however, the ubiquitination mechanism of STAT3 in CRC is still unclear, which stimulated further research on STAT3 ubiquitination.