Expression Of Histone Demethylase KDM6A In Oral Squamous Cell Carcinoma Study On The Mechanism Of Action

Objectives:The purpose of this study is to detect the expression and biological function of KDM6 A in oral squamous cell carcinoma.To explore the possible regulatory signal pathway and the effect of KDM6 A on the expression level of target gene,and to elucidate the mechanism of the KDM6 A in the development of oral squamous cell carcinoma.It is divided into the following two points:1.Study on the role of KDM6 A in the development of oral squamous cell carcinoma.2.To explore the molecular mechanism of KDM6 A regulating the proliferation and migration of oral squamous cell carcinoma.Research methods:1.The expression and mutation of KDM6 family in oral squamous cell carcinoma(OSCC)were analyzed by bioinformatics,and the clinicopathological parameters were analyzed.2.Immunohistochemical staining was used to detect the expression of KDM6 A in oral squamous cell carcinoma tissue microarray.3.The effects of KDM6 A on the proliferation and migration of oral squamous cell carcinoma cells were studied in vitro,including CCK8,EDU proliferation,scratch repair,Transwell migration.4.Differential gene clustering,GO functional enrichment analysis and KEGG analysis were used to search for the signal pathway and target gene regulated by KDM6 A.Results:1.Bioinformatics analysis showed that the expression of KDM6 A in OSCC was significantly lower than that in normal oral tissues.The mutation frequency of KDM6 A was 7%,KDM6 B was 1.9%,UTY was not found.The expression of KDM6 A in female patients was higher than that in male patients.UTY was mainly expressed in male patients,but the expression of KDM6 B was not correlated with gender.The expression of KDM6 A and UTY was significantly correlated with the survival time of the patients,but the analysis of KDM 6B had no statistical significance.The expression of KDM6 A m RNA was negatively correlated with the malignancy of oral squamous cell carcinoma.2.Tissue microarray immunohistochemical staining of oral squamous cell carcinoma showed that the expression of KDM6 A was lower in cancer tissues than in normal oral tissues.3.Cell assay showed that knockdown of KDM6 A promoted the proliferation and migration of OSCC,while overexpression of KXM6 A inhibited it.4.RNA-Seq sequencing showed that 1462 genes were differentially expressed after KDM6 A knockdown,of which 605 were down-regulated and 857 were up-regulated.The KEGG enrichment analysis of differential genes combined with bioinformatics analysis revealed that KDM6 A may play a tumor suppressor role by regulating its downstream gene GSK3 B through Hippo singaling pathway.Conclusion:The expression of KDM6 A was low in oral squamous cell carcinoma,and its high expression was associated with better prognosis.KDM6 A inhibits the proliferation and migration of oral squamous cell carcinoma in vitro.KDM6 A may regulate GSK3 B through Hippo signaling pathway to play a role in tumor suppression.