Objective:To investigate the effects of matrix metalloproteinase 10(MMP10)on the proliferation,migration,invasion,and lymph node metastasis of oral squamous cell carcinoma(OSCC)cells,and to explore the underlying mechanisms.Methods:Gene expression profile data and survival data of head and neck squamous cell carcinoma(HNSCC)tissues and adjacent non-cancerous tissues were downloaded from The Cancer Genome Atlas(TCGA).Protein expression profile data of HNSCC tissues and adjacent non-cancerous tissues were downloaded from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)database,and select the data of OSCC from HNSCC.The data from public database were used to analyze the differences in MMP10 expression at the mRNA and protein level between HNSCC/OSCC tissues and adjacent non-cancerous tissues,and to analyze the impact of MMP10 expression level on the survival rate of HNSCC patients,as well as the impact of human papillomavirus(HPV)on MMP10 gene expression in HNSCC patients.MMP10 expression level in 52 pairs of OSCC tissue samples and adjacent non-cancerous tissue samples(from the First Affiliated Hospital of Fujian Medical University)was measured by real-time quantitative PCR.After silencing MMP10 expression using siRNA(siMMP10-1291 and siMMP10-1336),the effect of MMP10 on the proliferation ability of OSCC cells was detected by CCK-8 assay and colony formation assay.The effects of MMP10 on the migration and invasion abilities of OSCC cells was assessed by wound-healing assay and transwell assay,respectively.To verify the effect of MMP10 knocking down on lymph node metastasis of OSCC cells in vivo,we constructed a nude mouse tongue cancer orthotopic model by shRNA(shMMP10-1291 and shMMP10-1336).Differential expression genes associated with MMP10 were screened from the gene expression profile data of OSCC patients in the TCGA database,and pathway enrichment analysis was performed using the GSEA software to further analyze the correlation between MMP10 and genes from the significantly enriched pathway.Results:Compared with adjacent non-cancerous tissues,the expression level of MMP10 in HNSCC and OSCC tissues was significantly increased(P<0.000 1),and HNSCC patients with high MMP10 expression had a lower survival rate(HR=1.32,P=0.04).HNSCC patients in the HPV-group had higher MMP10 gene expression levels(P<0.000 1),but their survival rate was significantly lower than that of HNSCC patients in the HPV+group(HR=0.48,P=0.004).Downregulating MMP10 expression could inhibit the migration,invasion and lymph node metastasis in vivo of OSCC cells.In OSCC patients,differentially expressed genes associated with MMP10 were significantly enriched in the Wnt signaling pathway(NES=1.505,P=0.029),and multiple genes in the Wnt signaling pathway,including WNT3,WNT3A,WNT5A,and WNT5B,were positively correlated with the expression level of MMP10.Conclusion:MMP10 promotes the invasion,metastasis and lymph node metastasis in vivo of OSCC cells by regulating the Wnt signaling pathway.

Objective:To investigate the effects of matrix metalloproteinase 10(MMP10)on the proliferation,migration,invasion,and lymph node metastasis of oral squamous cell carcinoma(OSCC)cells,and to explore the underlying mechanisms.Methods:Gene expression profile data and survival data of head and neck squamous cell carcinoma(HNSCC)tissues and adjacent non-cancerous tissues were downloaded from The Cancer Genome Atlas(TCGA).Protein expression profile data of HNSCC tissues and adjacent non-cancerous tissues were downloaded from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)database,and select the data of OSCC from HNSCC.The data from public database were used to analyze the differences in MMP10 expression at the mRNA and protein level between HNSCC/OSCC tissues and adjacent non-cancerous tissues,and to analyze the impact of MMP10 expression level on the survival rate of HNSCC patients,as well as the impact of human papillomavirus(HPV)on MMP10 gene expression in HNSCC patients.MMP10 expression level in 52 pairs of OSCC tissue samples and adjacent non-cancerous tissue samples(from the First Affiliated Hospital of Fujian Medical University)was measured by real-time quantitative PCR.After silencing MMP10 expression using siRNA(siMMP10-1291 and siMMP10-1336),the effect of MMP10 on the proliferation ability of OSCC cells was detected by CCK-8 assay and colony formation assay.The effects of MMP10 on the migration and invasion abilities of OSCC cells was assessed by wound-healing assay and transwell assay,respectively.To verify the effect of MMP10 knocking down on lymph node metastasis of OSCC cells in vivo,we constructed a nude mouse tongue cancer orthotopic model by shRNA(shMMP10-1291 and shMMP10-1336).Differential expression genes associated with MMP10 were screened from the gene expression profile data of OSCC patients in the TCGA database,and pathway enrichment analysis was performed using the GSEA software to further analyze the correlation between MMP10 and genes from the significantly enriched pathway.Results:Compared with adjacent non-cancerous tissues,the expression level of MMP10 in HNSCC and OSCC tissues was significantly increased(P<0.000 1),and HNSCC patients with high MMP10 expression had a lower survival rate(HR=1.32,P=0.04).HNSCC patients in the HPV-group had higher MMP10 gene expression levels(P<0.000 1),but their survival rate was significantly lower than that of HNSCC patients in the HPV+group(HR=0.48,P=0.004).Downregulating MMP10 expression could inhibit the migration,invasion and lymph node metastasis in vivo of OSCC cells.In OSCC patients,differentially expressed genes associated with MMP10 were significantly enriched in the Wnt signaling pathway(NES=1.505,P=0.029),and multiple genes in the Wnt signaling pathway,including WNT3,WNT3A,WNT5A,and WNT5B,were positively correlated with the expression level of MMP10.Conclusion:MMP10 promotes the invasion,metastasis and lymph node metastasis in vivo of OSCC cells by regulating the Wnt signaling pathway.