Correlations between the expression of ERK pathway mediated by NETO2 and metastasis and prognosis of oral squamous cell carcinoma

LU Xun-xun; WEI Shu-ping; WEI Fu-gui

doi:10.13820/j.cnki.gdyx.20230398

Abstract：Objective To investigate the clinical significance of neuropilin and tolloid-like 2(NETO2)in oral squamous cell carcinoma(OSCC)and the effect of its knockdown on OSCC cell proliferation,migration and invasion.Methods NETO2 expression in OSCC and non-OSCC tissues of OSCC patients was analyzed using Gene Expression Profile Interaction Analysis(GEPIA),and the correlation of NETO2 expression with overall survival in OSCC patients was analyzed.From November 2020 to January 2022,124 cancer specimens and matched normal tissues(5cm from the tumor edge)were obtained from our hospital.NETO2 expression was analyzed by Western blotting.In in vitro experiments,HSC-4 cells were divided into NETO2 knockdown(sh1,sh2)group and corresponding control(NC)group.The effects of NETO2 on HSC-4 cell proliferation,invasion and migration were investigated using CCK-8,clone formation and Tr-answell assays.In addition,rescue experiments were performed by adding an ERK agonist(EGF)to NETO2-knockdown HSC-4 cells.Results The expression of NETO2 in OSCC tissues was abnormally high,and the prognosis of OSCC pa-tients with high NETO2 expression was poor.Compared with the NC group,the cell viability,colony-forming ability,and the number of migrating and invasive cells in the sh1 and sh2 groups were significantly decreased(P＜0.05).Gene Set Enrichment Analysis(GSEA)of Gene Ontology(GO)revealed that knockdown of NETO2 in OSCC cells resulted in significant changes in ERK signaling pathway gene expression.Compared with sh1 group,sh1+EGF group increased the expression of ERK in NETO2 knockdown cells(P＜0.05).In addition,the growth,colony formation ability,migration and invasion of NETO2 knockdown OSCC cells in the sh1+EGF group were significantly higher than those in the sh1 group(P＜0.05).Conclusion High levels of NETO2 expression in OSCC tissues are associated with poor patient out-comes.NETO2 is an important oncoprotein that may activate the ERK signaling pathway to promote the proliferation,inva-sion and metastasis of OSCC cells.