| Background:Oral squamous cell carcinoma(OSCC)is the most common malignant tumor in the oral and maxillofacial region.At present,the domestic incidence of OSCC is increasing year by year.Although the overall survival time of OSCC patients has improved at this stage,the 5-year overall survival rate of patients is still about 50%,and that of patients with advanced stage is even lower.Therefore,it is of great significance to elucidate the important molecular mechanisms in the occurrence and development of OSCC and explore promising therapeutic targets for OSCC.Ubiquitin proteasome system(Ubiquitin Proteasome System,UPS)plays an important role in the clearance of waste proteins and cell cycle regulation.its activity is enhanced in cancer cells.The 26S proteasome subunit ATPase 4(proteasome 26S subunit,ATPase 4,PSMC4)is an essential member of the 19S regulatory granule in the 26S proteasome,which affects cell growth and differentiation.Studies have found that PSMC4 is related to the development and prognosis of tumors such as breast cancer and endometrial cancer.In recent years,the role of USP-related gene families in cancer has gradually become a research hotspot.However,the expression changes and role of PSMC4 in OSCC have not been reported yet.This study aims to explore the relationship between the expression changes of PSMC4 in OSCC and the prognosis and clinicopathological characteristics of OSCC patients,and to further investigate the biological function of PSMC4 in OSCC in vivo and in vitro.Methods:1.Investigate the expression changes and prognostic significance of PSMC4 in OSCCUsing bioinformatics analysis and public databases,we studied the mRNA and protein expression changes of PSMC4 in OSCC and analyzed their correlation with the prognosis of OSCC patients.Immunohistochemical staining,Western blot,qRT-PCR and other methods were used to study the expression changes of PSMC4 in OSCC clinical samples and OSCC cell lines,and to verify the database analysis results.In order to explore the possible regulatory mechanism of PSMC4 in OSCC,GSEA enrichment analysis was performed on the genes in the TCGA database.2.Investigate the effect of PSMC4 on the biological phenotype of OSCC cellsThe expression of PSMC4 was knocked down by siRNA technology,and the changes of tumor cell proliferation,migration,invasion,cell cycle and apoptosis were explored by CCK-8 experiment,scratch experiment,Transwell experiment and flow cytometry.3.Explore the effect of PSMC4 on the growth of OSCC in nude miceThe PSMC4 interference plasmid was transfected with lentivirus to construct a Cal-27 cell line stably knocking down PSMC4,and then the subcutaneous tumorigenesis experiment was carried out in nude mice.The transplanted tumors were stained with HE to observe the growth of tumor cells.The expression of the proliferation index Ki67 protein in the tumor was detected by immunohistochemical technique.Results:1.The mRNA and protein of PSMC4 were highly expression in OSCC and most tumors.Patients with high expression of PSMC4 had shorter overall survival and worse prognosis.The expression changes of PSMC4 were related to the gender and clinical stage of OSCC patients.The expression level of male was higher than that of female and middle and late clinical stage was higher than that of early stage.PSMC4 can be used as a prognostic factor for OSCC patients.In OSCC,PSMC4 might participate in the regulation of DNA damage repair,PI3K/AKT/mTOR,cell cycle G2/M checkpoint,mTORC1,P53,apoptosis and other signaling pathways and biological processes;.2.PSMC4 promoted the proliferation,migration and invasion of OSCC cells,inhibited cell apoptosis,regulated cell cycle,and promoted cell division and proliferation in vitro.3.PSMC4 promoted the growth of OSCC in vivo.Conclusion:1.The high expression of PSMC4 in OSCC indicates the poor prognosis of patients.PSMC4 can be used as a prognostic factor for OSCC patients.2.PSMC4 is a tumor-promoting gene of OSCC,which can promote the progression of OSCC in vitro and in vivo. |
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