Recent studies provided strong support for the view that ubiquitin-specific 
protease 22 (USP22) plays a central role in cell-cycle progression and also in 
pathological processes such as oncogenesis. We have recently shown that USP22 
levels are elevated in colorectal carcinoma with associated increase in the 
expression of several cell-cycle-related genes. However, the precise mechanism 
for these functions of USP22 at molecular level has not been fully elucidated. 
Currently, we investigated the role of USP22 in human colorectal cancer (CRC). 
We observed that USP22 expression was statistically significantly correlated 
positively with that of BMI-1, c-Myc and both, pAkt (Ser473), and pAkt (Thr308), 
in primary tumor tissues from 43 CRC patients. Down-regulation of USP22 
expression in HCT116 colorectal cancer cells by siRNA resulted in the 
accumulation of cells in the G1 phase of the cell cycle. RNAi-knockdown of USP22 
in HCT16 cells also led to the repression of BMI-1 and was accompanied by the 
up-regulation of p16INK4a and p14ARF, with a consequent decrease in E2F1 and p53 
levels. In addition, down-regulation of c-Myc-targeted cyclin D2 was also 
noticed in cells treated with USP22-siRNA. Furthermore, our results showed that 
USP22 deletion also caused down-regulation of Akt/GSK3β activity, which can also 
contribute to the reduction of cyclin D2. Collectively, our current results 
suggest that USP22 may act as an oncogene in CRC as it positively regulates cell 
cycle via both BMI-1-mediated INK4a/ARF pathway and Akt signaling pathway.