The Function And Molecular Mechanism Of Transcription Factor ZFP57 In Promoting The Development Of Ovarian Cancer

Objectives Ovarian cancer ranks first in the mortality rate of gynecological cancer,which seriously endangers women’s health and life.It has the characteristics of high recurrence rate,high metastasis rate and low survival rate.It is an urgent medical problem to improve the overall treatment effect and reduce the mortality of ovarian cancer.At present,the pathogenesis and specific etiology of ovarian cancer are unknown.However,the research on the relationship between DNA methylation of epigenetic modification and the abnormal expression of specific epigenetic inhibitor zinc finger protein and the occurrence,progression and prognosis of cancer has attracted more and more attention.we found that the transcription factor ZFP57 was closely related to DNA methylation through screening in the bioinformatics database,It is highly expressed in ovarian cancer and is associated with poor prognosis of ovarian cancer patients.This study further analyzed the expression and clinicopathological characteristics of ZFP57 in ovarian cancer tissues,demonstrated the biological function of ZFP57 in ovarian cancer cell lines,and explored the possible molecular mechanism of ZFP57 in the development of ovarian cancer,in order to provide new ideas for the treatment of ovarian cancer.Methods 1.The database was used to screen out the target gene transcription factor ZFP57 related to DNA methylation and ovarian cancer prognosis,and CO-IP experiments demonstrated that it was closely related to DNA methylation.2.The expression of ZFP57 in ovarian cancer was analyzed by database,and the expression level of ZFP57 was detected by immunohistochemistry on ovarian cancer tissue chip,and the relationship between ZFP57 and clinicopathological characteristics was analyzed.3.Select ovarian cancer cell lines,construct stable overexpression and transient interference cell lines,and carry out CCK-8 experiment,clone formation experiment,nude mouse tumorigenesis experiment,scratch experiment,Transwell experiment,apoptosis experiment to detect the effect of ZFP57 on proliferation,migration and apoptosis.4.RNA-Seq technology and KEGG enrichment were used to analyze the regulatory pathway of ZFP57 in ovarian cancer,the Cistrome Data Browser database and ChiIP-Seq data were used to screen downstream target genes,and RT-PCR,Western-Blot,flow cytometry,Luciferase double luciferase assay were used to verify the results.Results 1.CO-IP experiments revealed that transcription factor ZFP57 regulates DNA methylation by acting on methyltransferase.2.Multiple databases have found that ZFP57 is highly expressed in ovarian cancer and correlated with prognosis.Immunohistochemical test showed that ZFP57 was highly expressed in ovarian cancer tissue,and its high expression was related to the clinical stage and pathological grade of the tumor.The higher the expression of ZFP57,the later the clinical stage,the higher the pathological grade,and the worse the prognosis of ovarian cancer patients.3.CCK-8 assay,clone formation assay and tumor formation assay in nude mice showed that high expression of ZFP57 promoted the proliferation of ovarian cancer cells.Scratch assay and Transwell assay showed that high expression of ZFP57 promoted the migration ability of ovarian cancer cells,and apoptosis assay showed that high expression of ZFP57 inhibited the apoptosis of ovarian cancer cells.4.The results of flow cytometry,RT-PCR and Western-Blot showed that ZFP57 regulated the ovarian cancer cell cycle,and the overexpression of ZFP57 promoted the cells to enter the DNA synthesis phase.The cells arrested in G1 phase were significantly reduced,and the expressions of cell cycle key proteins CCNA2,CCNE2 and CDC7 were significantly increased.The expression of kinase inhibitor p21 was significantly reduced.5.Luciferase double luciferase assay,RT-PCR and Western-Blot found that ZFP57 directly transcribes and regulates the expression of BRCA1,and the high expression of ZFP57 promotes the expression of BRCA1,thus regulating the cell cycle.Conclusions 1.The transcription factor ZFP57 is closely related to DNA methylation,and its molecular background is reliable.2.ZFP57 is highly expressed in ovarian cancer tissues,which is closely related to poor prognostic factors(clinical stage,pathological grade,etc.)of ovarian cancer,and is a good biomarker for evaluating prognosis and predicting recurrence.3.ZFP57 can promote the proliferation and migration of tumor cells and inhibit apoptosis in ovarian cancer.4.ZFP57 regulates the cell cycle of ovarian cancer through BRCA1,which may be the mechanism to promote the occurrence and development of ovarian cancer.5.ZFP57 is expected to become a new target for ovarian cancer treatment.