Inflammasome NLRP6 Inhibits Colorectal Cancer Via P53 Pathway

Objective:We investigated the role of inflammasome NLRP6 and P53 in colorectal cancer.Methods:We downregulated NLRP6 in the colorectal cancer cell lines HCT116 P53 WT(WT)and HCT116 P53-/-(KO).The NLRP6 knockdown efficiency was performed by Real-Time PCR and Western Blot.The proliferation,migration and apotosis was detected by CCK-8,Transwell and Flow cytometry.The protein level was detected by Western Blot.Results:The stable cell lines,WT CTRL,WT NLRP6-ShRNA,KO CTRL and KO NLRP6-ShRNA,were successfully constructed.The NLRP6 knockdown efficiency was more than 70%.Knockdown NLRP6 promoted the proliferation and migration in both WT and KO cells;and the proliferation and migration of KO NLRP6-ShRNA was significantly higher than that of WT NLRP6-ShRNA.We found that NLRP6 was expressed in the cytoplasm by Immunofluorescence.After knockdown NLRP6,the apoptosis of colorectal cancer cells decreased.Compared with WT CTRL,the expression level of NF-?B?MDM2?Cyclin B1 was higher and the expression level of P53 and P21WAF1/CIP1 were reduced in WT NLRP6-ShRNA;compared with KO CTRL,the expression level of Cyclin B1 increased and the expression level of NF-?B,MDM2 and P21WAF1/CIP1 were reduced.Conclusions:Knockdown NLRP6 significantly promoted proliferation and migration in P53 wildtype and knockout cell lines.NLRP6 promoted the apoptosis of colorectal cancer cells.Inflammasome NLRP6 may inhibit colorectal cancer by regulating NF-?B,MDM2,P53,P21WAF1/CIP1,Cyclin B1.