High Expression Of FKBPL May Be Associated With Poor Prognosis And Related To Proliferation,Cell Cycle And Apoptosis In DLBCL

PurposeOur study aimed to analyze the expression of FKBP Prolyl Isomerase Like(FKBPL)in diffuse large B cell lymphoma(DLBCL)and the relationship between the expression of FKBPL and the clinical prognosis of DLBCL patients.Then,the effect of downregulation of FKBPL influencing the cell proliferation in DLBCL were investigated,which might provide scientific evidence for the development of FKBPL as the target of lymphoma targeted therapy strategy.MethodsAt first,GEPIA2(Gene Expression Profiling Interactive Analysis 2)database was used to the analyzed the differential expression of FKBPL gene in 31 common human tumor tissues.CCLE(Cancer Cell Line Encyclopedia)database was used to analyze the differential expression of FKBPL gene in tumor cell lines from different tissue sources(including DLBCL cell lines).The microarray data of open clinical samples from Oncomine database,GEO database and GEPIA2 database were used to analyze the differential expression of FKBPL gene in DLBCL patients and normal lymph nodes.The relationship between the differential expression of FKBPL in tumor tissues of DLBCL patients and clinical prognosis was analyzed by open gene expression profile data in Genomic Scape database.The STRING database is used to predict the protein-protein interaction network(PPI)of the FKBPL gene.The first 500 genes most closely related to FKBPL gene were downloaded from GEPIA2 database and enriched and analyzed by Metascape database.Then,we chose 46 paraffin-embedded specimens of DLBCL at the department of pathology of the First Affiliated Hospital of Jinan University.Immunohistochemistry(IHC)staining was performed on all DLBCL cancer tissues and non-tumor lymph node tissue,so as to observe whether there was any difference in FKBPL levels between cancer tissues and normal lymph node tissue.We used RT-q PCR to detected the expression of FKBPL m RNA in different diffuse large B-cell lymphoma cells,and selected the DLBCL cell lines with high expression of FKBPL.After DLBCL cell line(SUDHL-6)was infected with FKBPL sh RNA lentivirus,the transfection efficiency of SUDHL-6 cells was observed by inverted fluorescence microscope.The cells stably expressing FKBPL-sh RNA were constructed.We used CCK8 to detected the proliferation ability of SUDHL-6 cells infected by FKBPL sh RNA lentivirus,and used Flow cytometry to detected cell cycle and apoptosis.Results1.Analysis of the data from the open database,it is found that the FKBPL is significantly overexpressed in most human tumor tissues.Gene differential expression analysis showed that FKBPL was significantly higher in DLBCL than that in normal lymph nodes.Survival analysis showed that DLBCL patients with high expression of FKBPL had a shorter overall survival.2.The expression of FKBPL protein in DLBCL tumor tissue and non-tumor lymph node tissue section was analyzed by immunohistochemical.The results showed that the expression of FKBPL was increased in tumor tissues of patients with DLBCL.3.After SUDHL-6 cells were infected with lentivirus FKBPLsh RNA,RT-q PCR detection showed that the expression of FKBPL at m RNA level was significantly decreased,and Western-Blot detection showed that the expression of FKBPL protein was significantly decreased.CCK8 assay showed that the proliferation of SUDHL-6 cells was inhibited after the decrease of FKBPL expression.The results of cell cycle detection showed that compared with the control group,the percentage of G0/G1 phase cells in SUDHL-6 cells increased significantly after the decrease of FKBPL expression.Flow cytometry detection of apoptosis showed that compared with the control group,when the expression of FKBPL decreased,the apoptosis rate of SUDHL-6 cells increased significantly.Conclusion1.Bioinformatics analysis showed that FKBPL was significantly overexpressed in DLBCL,and the higher the expression of FKBPL in tumor tissues of DLBCL patients,the worse the prognosis.2.Immunohistochemical analysis showed that FKBPL was significantly overexpressed in tumor tissues of patients with DLBCL.3.Downregulation of FKBPL expression can inhibit the proliferation of DLBCL cells,block the cell cycle in G0/G1 phase,and induce apoptosis.