The Expression And Biological Function Of ZBTB16 In Breast Carcinoma

Objective:This study explored the expression,prognosis,clinicopathological parameters and co-expression genes of zinc finger and BTB domain containing 16(ZBTB16)in patients with breast cancer(BC)by using public database,in order to illustrate its prognosis and potential therapeutic value.In addition,the biological role of ZBTB16 in the progression of BC was clarified through the cell function experiment,which provided a new basis for the clinical diagnosis and treatment of BC and laid a foundation for the exploration of the mechanism of BC occurrence and development.Method:1.Through literature review,ZBTB16 was selected as the target protein.Based on the public database,this study conducted a bioinformatics analysis of ZBTB16 to investigate whether ZBTB16 can be used as a prognostic indicator of BC.The mRNA expression pattern of ZBTB16 in BC was studied by Oncomine database.The relationship between the gene expression level and clinicopathological and molecular characteristics was analyzed using the bc-Genexminer v4.4 database.Kaplan Meier Plotter database was used to determine the prognostic value of ZBTB16 in BC patients.The genes co-expressed with ZBTB16 were identified by cBioPortal analysis.The ClueGo plug-in in the software of Cytoscape was used to analyze and predict its potential function in BC.2.The differential expression of ZBTB16 was confirmed by Western blot.3.ZBTB16 overexpressed stable cell lines and silencing cell lines were constructed,and the effects of ZBTB16 on proliferation,invasion,migration and apoptosis of BC cells were investigated by CCK8,Transwell and Annexin V-PE cell apoptosis experiments.Result:1.In this study,we conducted a comprehensive bioinformatics analysis of ZBTB16.Compared with normal breast tissue,ZBTB16 mRNA level in BC decreased significantly.The decrease of ZBTB16 expression is closely related to clinicopathological features,including: > 51 years old,lymph node metastasis,estrogen receptor(ER)and progesterone receptor(PR)negative,HER2 positive,basal cell like breast cancer,triple negative breast cancer,mutant p53 and higher Scarff bloom Richardson(SBR)grade.The down-regulation of ZBTB16 mRNA was associated with poor overall survival(OS),relapse free survival(RFs),distant metastasis free survival(DMFS)and metastatic relapse free survival(MRFS)in BC patients.Moreover,the expression of ZBTB16 mRNA in BC was positively correlated with the expression of SLC26A3.Its main function in BC may be related to the regulation of the cell cycle and mitotic sister chromatid segregation,and it is speculated that it may exert its anticancer effect through the related signaling pathways mentioned above.2.The reslut of Western blot showed that the protein expression of ZBTB16 in BC decreased significantly.3.We successfully constructed ZBTB16 stable overexpression and silenced cell lines.RT-PCR and Western blot analysis confirmed the overexpression and silencing effect of ZBTB16.The results of cell function experiment showed that after overexpression of ZBTB16,the ability of migration,invasion and proliferation of BC cells was significantly weakened,while the ability of apoptosis was significantly enhanced;after silencing ZBTB16,the ability of migration,invasion and proliferation of BC cells was significantly enhanced,while the ability of apoptosis was significantly weakened.Conclusion:1.The down-regulated expression of ZBTB16 in BC is associated with poor prognosis and malignant progression.This gene might be a valuable tumor biomarker and a potential therapeutic target with co-expressed SLC26A3 gene in BC.2.The expression of ZBTB16 inhibited the proliferation,invasion and migration of BC cells,but promoted apoptosis.