Study On The Mechanism Of Transcription Factor SRF And Histone Acetylation Regulating The Expression Of Integrin β6 In OSCC

Objective:Integrin β6 is highly expressed in OSCC and is closely related to tumor invasion and metastasis,but the specific regulatory mechanism is unknown.Since the regulation of gene expression is closely related to the activation of transcription factors and histone acetylation modification,this study intends to study the activation of transcription factors and histone acetylation modification that affect the expression of integrin β6,to explore the specific molecular mechanism of high expression of integrinβ6 in oral squamous cell carcinoma.Methods:Immunohistochemical method was used to detect the expression of integrin β6 in OLK,OSCC and normal tissues.After overexpression of β6 in oral leukoplakia cells,the proliferation and migration ability of cells was detected.Luciferase reporter gene assay was used to detect the existence of SRF binding site in integrin β6 promoter region.The effects of SRF,CBP and histone acetylation on integrin β6 were detected in oral squamous cell carcinoma cells.The histone acetylation status,SRF and CBP recruitment in integrin β6 promoter region were detected by CHIPs.An animal model of malignant transformation of oral leukoplakia was established,and the regulation of integrin β6 by SRF was detected at animal level.Results:1 The expression of integrin β6 in oral leukoplakia and oral squamous cell carcinoma was higher than that in normal tissues.2 In oral leukoplakia cells,overexpression of integrin β6 promoted cell proliferation and migration.3 Transcription factor SRF,histone acetylation,acetylase CBP promotes the expression of integrin β6 by regulating the transcriptional initiation region of integrinβ6 in oral squamous cell carcinoma cells.4 In the mouse model of malignant transformation of mucosal leukoplakia induced by 4NQO,the binding of SRF to integrin β6 promoter increased in tumor tissue.