The Expression And Correlation Analysis Of Chemokine CXCL3 In Oral Squamous Cell Carcinoma

Objective: This study principally evaluated the m RNA and protein levels of CXCL3 in oral and squamous cell carcinoma tissues and elucidated its mechanism.To investigate the effect of upregulation of CXCL3 on the degree of malignancy in human oral squamous cell carcinoma HSC-4 cells.Methods: Using R language and Perl script,multiple databases were used to specify the difference expression,prognosis and potential signaling pathways of CXCL3 in oral and squamous cell carcinoma tissues.In addition,the distribution of CXCL3 protein and its correlation with patient data were appraised by immunohistochemical assay on oral tissue chip.Finally,stably transfected and simulated CXCL3-transfected HSC-4 cells were constructed for CCK-8,flow cytometry,Transwell migration assay and nude mouse transplantation experiment to analyze the tumor biological effects of CXCL3 on the proliferation efficiency,apoptosis level and migration potency of HSC-4 cells in vitro and in vivo.Western Bolt technology verified the expression of key genes in the signal pathway obtained by bioinformatics analysis.Results: The sequencing data from multiple databases displaied that CXCL3 expression levels were significantly increased in patients with oral squamous cell carcinoma compared with normal tissues.Kaplan-meier analysis and Cox regression model further confirmed that the higher the m RNA transcription level of CXCL3 in patients,the lower the overall survival rate and could be used as a special indicator for clinical evaluation of oral squamous cell carcinoma patients.KEGG analysis using gene enrichment analysis demonstrated that Jak-STAT signaling pathway,cytokine-cytokine receptor interaction,MAPK signaling pathway and apoptosis may be primary regulatory pathways involved in CXCL3 malignancy.Immunohistochemical results also hinted that CXCL3 score in oral squamous cell carcinoma was significantly higher than that in normal tissues,and the upregulation level was typically essential to stage and lymph node metastasis.CCK-8,Transwell and Flow cytometry displaied that CXCL3 could extremely accelerate the proliferation and invasion of HSC-4 cells and cut down the apoptosis of HSC-4cells.In addition,the growth rate of HSC-4 cells overexpressing CXCL3 in nude mice was extremely accelerated.Meanwhile,Western Bolt detected the expression of primary genes involved in the above signaling pathway and found that HSC-4 cells with upregulated CXCL3 expression decreased Bax and caspase9 expression,while the expression of Bcl-2,p-STAT3,NF-κ b p65,p-ERK and STAT3 increased in different degrees.Subsequent use of ERK1/2blocker PD98059 disclosed that abnormal growth and excessive invasion of HSC-4 cells caused by abnormal expression of CXCL3 were inhibited,indicating that MAPK was the primary signal pathway.Conclusion: CXCL3 expression is elevated in oral squamous cell carcinoma and the degree of elevation affects the abnormal behavior of tumors,while MAPK is an important signal transduction pathway in regulating the evolution of a series of lesions of tumor cells.