FKBP11 Promotes Cell Proliferation And Tumorigenesis Via P53 Related Pathways In Oral Squamous Cell Carcinoma

Objective:To investigate the expression of FK-506 binding protein 11(FKBP11)and the effect of FKBP11 on the cell proliferation in oral squamous cell carcinoma(OSCC),then explore the possibly regulator mechanism.Methods:Western blotch(WB)was utilized to analyze the expression of FKBP11 in human OSCC and para-cancerous normal tissues.Within the in vitro explore,the expression of FKBP11 in CAL-27,SCC-25 and SCC-15 cell lines was identified by WB,real-time fluorescence quantitative PCR(RT-PCR),and the appropriate cell line was chosen for follow-up explore.At that point small interfering RNA(si RNA)was utilized to knock down FKBP11,and after that in vitro tests,cell proliferation was assessed by high content screening(HCN),CCK-8,plate cloning,flow,Hoechst 33,258 recoloring and Calcein-AM/PI staining,and the expression of cell cycle arrest-and apoptosis-related proteins was recognized by WB.At that point the key qualities of flag pathways that can cause cell cycle arrest were identified by RT-PCR,and the pathways with the foremost self-evident changes were chosen for follow-up ponder.By utilizing the flag pathway inhibitor to pretreat the cells,the expression of cell cycle arrest-and apoptosis-related proteins was identified by WB again.In vivo experiment,the tumor volume and weight of nude mice were watched by intratumoral injection of si-RNA.Results:WB appeared that the expression of FKBP11 in OSCC was essentially higher than that in para-cancerous normal tissues(P<0.001),recommending that it plays an oncogene part within the event and improvement of OSCC.The characteristics of high expression of FKBP11 in CAL-27 cell line were affirmed in vitro.After FKBP11 knockdown,the capacity of cell expansion and colony arrangement diminished(P<0.05).Flow cytometry appeared that the cell cycle was arrested in G2/M phase(P<0.05).The expression of cell cycle arrest-related protein CDK1 and Cyclin B1 diminished altogether,whereas the expression of p21 and p27 expanded essentially(P<0.05).At the same time,Hoechst 33,258 staining and Calcein-AM/PI staining showed that the number of apoptosis cells was significantly increased after FKBP11 knockdown.Flow cytometry appeared that the extent of early and late apoptosis cells expanded altogether after FITC/PI twofold staining(P<0.05).The expression of apoptosis-related protein Caspase-3 and Bax increased and the expression of Bcl-2 decreased(P<0.05).The comes about of RT-PCR appeared that the alter of p53 was the foremost noteworthy after FKBP11 knockdown(P<0.05).In expansion,p21 and p27 were essentially down-regulated with the diminish of p53 expression after the utilize of PFT-α(P<0.05).CDK1 and Cyclin B1,which were already stifled,were essentially turned around,whereas the expression level of apoptosis-related proteins Caspase-3,Bax and Bcl-2 was essentially switched.The expression level of Bcl-2 was moreover essentially turned around(P<0.05).In vivo experiment,WB showed that the expression of FKBP11 in tumor tissue of the experimental group decreased significantly(P<0.05),which demonstrated that the creature demonstrate of FKBP11 knockdown was effective.In addition,compared with the negative control group,the tumor volume and weight within the exploratory gather were significantly smaller than those within the negative control group(P<0.05).Conclusion:FKBP11 plays an oncogene part in OSCC,which may control cell cycle progression and apoptosis to promote cell proliferation through p53/p21/p27 and p53/Bcl-2/Bax pathways.It is proposed that FKBP11 may be a modern candidate target for the treatment of OSCC.