The Mechanism Of Transcription Factor GATA4 Expression On The Metastasis Of Ovarian Cancer And Its Prognostic Value

Objective: Epigenetics plays an important role in the development of cancer.This article mainly uses bioinformatics methods to find transcription factors related to epigenetic reprogramming(GATA binding protein 4),and then mainly discusses how this transcription factor mediates the metastasis of ovarian cancer through histone methylation and its relationship to clinical outcomes in patients with ovarian cancer.Methods: The anti-H3K4me3 antibody was used to perform chromatin immunoprecipitation experiments on 10 fresh specimens of clinical high-grade serous ovarian cancer,10 normal ovaries and 10 normal fallopian tubes.The obtained samples were sequenced in order to find the transcription factor that is associated with epigenetic modifications.The effects of GATA4 on metastasis and invasion of ovarian cancer were examined using in vitro experiments(Transwell technique and colony formation assay)and in vivo experiments(animal model).Immunohistochemistry was used to detect the expression of GATA4 in normal fallopian tube tissues and ovarian cancer tissues.The analyses of gene expression profiling chips and TCGA database demonstrate the impact of GATA4 on clinical outcomes.Chromatin immunoprecipitation DNA detection technology and RNA sequencing technology were used to find downstream genes and pathways regulated by GATA4.Mass spectrometry and protein immunoprecipitation techniques were used to find proteins that interact with GATA4.Results: The expression of GATA4 in high-grade serous ovarian cancer is relatively lower than that in normal tissues.And it is closely related to the modification of H3K4me3 in ovarian cancer.The high expression of GATA4 can significantly extend the overall survivaltime and progression free survival time of patients and its low expression is also closely related to the FIGO stage and higher pathological grade of advanced ovarian cancer.GATA4 is capable of inhibiting metastatic invasion of ovarian cancer cells in vivo and in vitro.GATA4 can enhance the histone H3R2 symmetrical dimethylation by interacting with PRMT5 protein,and then enhance the H3K4me3 by recruiting H3K4 methyltransferase,and finally regulate the gene expression of downstream ADAM19.Conclusions: For the first time,we describe the relationship between GATA4 protein and the epigenetic reprogramming of ovarian cancer,and the relationship between GATA4 and clinical prognosis of ovarian cancer,and demonstrate that GATA4 regulates methylation of histone H3K4 by interacting with PRMT5,which will mediate the expression of the downstream gene ADAM19.It is suggested that GATA4 is likely to become a new target for clinical treatment of ovarian cancer in the future.