Validation And Mechanism Of Metastatic Related Gene Zwint In Prostate Cancer

BackgroundProstate cancer is a malignant tumor that occurs in male prostate tissue and is the result of abnormal disordered growth of prostate acinar cells.The incidence of prostate cancer has obvious geographical and ethnic differences.In developed countries such as Europe and the United States,it is the most common malignant tumor in men,and its mortality ranks second in various cancers.In Asia,its incidence rate is lower than Western countries,but in recent years it has shown a rapid upward trend.Prostate cancer poses a great threat to the health of middle-aged and elderly men.Clinical manifestations may include urinary disturbances,manifested as progressive dysuria,dysuria,urinary insufficiency,etc.In severe cases,urine drips and urinary retention occur.Cancer will metastasize when it develop to the later period,which causes more than 90%of cancer-related deaths,and most patients with prostate cancer(PCa)also die due to metastases.The "metastatic cascade" is a complex biological process that includes dissociation of tumor cells(from the primary tumor),local infiltration,intravascular invasion,circulatory transport,extravasation,colonization,and the growth of end organs.Although cancer-related deaths account for a large proportion of cancer patients,many biological procedures of this complex process are still unknown.This article downloads prostate cancer metastasis related data from the GEO database and prostate cancer mRNA data from the TCGA database;using R software to perform data mining and bioinformatics analysis of the expression of the two at the mRNA level,using the venny tool to analyze the related genes.Combined with the bioinformatics tool STRING database,the differentially expressed genes are common to the three data sets.The number of differential genes obtained from prostate metastasis related data sets GSE6919 and GSE32269 were 754 and 580,respectively.The differential analysis of TCGA-derived mRNA data obtained 3334 genes,and the analysis results of the three data sets were taken to obtain 55 differential genes,including Zwint.Gene expression is more significant in cancer metastasis samples.Zwint(ZW 10-interaction kinetochore protein 1)is a centromere-related protein,a substrate of the mitotic kinase Aurora B,which is a component of the centromere complex required for mitotic spindle checkpoints.It is involved in mitochondrial function and cell growth.It plays a role as a mitotic checkpoint in the cell division cycle.It can ensure that the chromosomes in the division period are evenly distributed to the newborn daughter cells,and prevent the chromosomes from producing chromosome aneuploidy.It is the main axis assembly.Required for checkpoint function.According to existing research reports,the down-regulation of Zwint expression inhibits cell proliferation in 293T cells and breast cancer MCF7 cells,and Zwint overexpression in human malignant tumors,including lung cancer,ovarian cancer,bladder cancer and breast cancer,and lung adenocarcinoma and ependymoma.However,in the progress of tumors,especially the functional role and mechanism of prostate cancer metastasis,it is still unclear.PurposeBiomass analysis was used to screen and identify genes related to prostate cancer metastasis,identify and screen genes closely related to prostate cancer invasion and metastasis,and explore the function and molecular mechanism of Zwint in prostate cancer invasion and metastasis.MethodsDownload prostate cancer metastasis related data from the GEO database and prostate cancer mRNA data from the TCGA database;use R software to perform data mining and bioinformatics analysis of the expression of the two at the mRNA level,and use the venny tool to analyze the relationship between the two.Combined with the bioinformatics tool STRING database,the differentially expressed genes are common to the three data sets.Finally,it was concluded that Zwint may be related to the migration of prostate cancer,and then the overexpression vector of Zwint was constructed to obtain PC3 and DU 145 cell lines that were stably expressed,and then the Zwint gene was knocked down by siRNA.Identify its invasion,migration and EMT-related functions,and initially explore its mechanism.Results1.First of all,we carried out bioinformatics analysis,and screened the prostate cancer metastasis database GSE6919 and GSE32269 to obtain Zwint genes closely related to prostate cancer metastasis.2.Compared with normal prostate tissue,the expression of Zwint in prostate cancer tissue is significantly increased,and it is positively correlated with the stage of prostate cancer disease.3.After obtaining virus stock solution from 293T packaging virus,we infected DU145 and PC3 cells respectively and successfully selected stable over-expressing cell lines,while using siRNA to knock down the expression of Zwint.Transwell migration and invasion experiments confirmed that overexpression of Zwint can promote the invasion and migration of prostate cancer,and knockdown inhibited its invasion and migration.And put forward the possible molecular mechanism.ConclusionThe results of this study demonstrate that overexpression of Zwint has a significant effect on the invasion and migration of prostate cancer cells PC-3 and DU145,and inhibition of Zwint can significantly inhibit its invasion and migration.