Bioinformatic Analysis Of Histone Deacetylase Inhibitors On Tumor Pathogenesis-Related Gene

At present,cancer is one of the chronic diseases that threaten human health,with high incidence,high mortality and high recurrence rate after cure.Existing studies have found that gene expression disorders closely related with tumor occurrence and development.Histone modification,such as methylation,acetylation,is one of the important ways to regulate gene transcription.In recent years,tumor inhibitors targeting histone deacetylase is one of the current research focus.At present,the anti-tumor molecular mechanism of histone deacetylase inhibitors and the downstream gene regulation network are unclear.Therefore,this study is based on the existing research of histone deacetylase inhibitor(HDACi),initially constructe the gene expression regulation network of tumor gene based on histone deacetylase inhibito through analysis,integration of a variety of database resources,and provide a new basis for molecular targeted therapy of clinical tumors.Method:1.In this study,by retrieving the data of HDACi-related tumor-associated genes,we mine the results of literature search using DIVID,STRING,Cytocaspe and transcription factor database,construct the gene map between he proteins and the most significant functional correlation module,and analyze the corresponding transcription factors in the module.2.By analyzing the data of SAHA-related tumor GEO expression profiles,We use the tumor-related genes that differently expressed under the influence of SAHA to constructe gene coding protein network diagram and significant functional correlation module by using BRB-array Tool,DIVID,STRING and Cytocaspe.3.The verification of the SAHA experiment initially proved that SAHA may affect the development of tumor cells through regulatory modules.Results:1.The GO function annotation and the KEGG pathway of the tumor-related genes related to HDACi,and six significant functional modules and transcriptionfactors were obtained through the literature search data mining.2.The GO function annotation and the KEGG pathway of the tumor-related genes related to SAHA,and four significant functional modules were obtained through the the gene chip data mining.3.SAHA validation experiments initially proved that SAHA may affect the development of tumor cells through regulating modules.Conclusion:1.HDACi can regulate a number of tumor-associated gene expression and cancer signaling pathways(such as TP53 signaling pathway),and Inhibit tumor cell proliferation and differentiation.2.The regulatory network formed by HDACi regulation of tumor-related genes synergistically inhibit the occurrence and development of tumors.3.The six significant especially with the transcription factor of the functional modules,may play an important role in the regulation tha HDACi inhibite tumor developing,such as HDAC3 functional modules.4.Transcription factors(TP53,MYC,SP1,JUN,etc.)regulated by HDACi and their related pathways may be an important target for tumor therapy.5.HDACi inhibites tumor cell proliferation by reducing BRCA1,BARD1 and RAD50 expression,and inhibiting DNA damage repair.