PRDX2 Promotes The Proliferation Of Colorectal Cancer Cells By Increasing The Ubiquitination Degradation Of P53

Objective: To explore the effect of PRDX2 on the proliferation of colorectal cancer cells,to clarify the relationship between PRDX2 and p53,and to clarify the specific mechanisms of PRDX2 on p53 ubiquitination.Methods: GEO and TCGA datasets were downloaded,bioinformatics analysis and KM analysis were carried out to detect the PRDX2 expression and the correlation with prognosis.HCT116 and LoVo cells were infected with lentivirus,and CCK-8,cell cycle,and colony formation experiment were used to elucidate the effect of PRDX2 on colorectal cancer cell proliferation in vitro.Western blot,immunofluorescence,RT-PCR were used to verify the correlation between PRDX2 and p53 in mRNA and protein level.The effects of PRDX2 on p53 ubiquitination and the mechanism were verified by co-immunoprecipitation and GST-pulldown.Xenograft tumor growth experiments were used to detect the inhibitory effect of PRDX2 on colorectal cancer cells in vivo.Results: PRDX2 is highly expressed in colorectal cancer tissues.Patients with high PRDX2 expression had a worse prognosis compared with those with low expression.Silencing PRDX2 inhibited the proliferation of HCT116 and LoVo cells,reduced the number and size of colonies,and blocked the cell cycle progression.Silencing PRDX2 increases the half-life of p53 and the p53 protein abundance.The specific mechanism is that PRDX2 could interact with RPL4,which competitively inhibits the binding of RPL4 and MDM2,which increases the level of p53 ubiquitination depended on degradation.Conclusion: PRDX2 increases the p53 ubiquitination-dependent degradation,which promotes the proliferation of HCT116 and LoVo cells in vitro and in vivo.