The Novel Prognostic Risk Factor STC2 Can Regulate The Occurrence And Development Of Osteosarcoma Through The Glycolytic Pathway

Background and purpose:Osteosarcoma,a highly aggressive malignant tumor of the bone,usually occurs in children and young adults.However,the considerable achievement in osteosarcoma’s clinical treatment in recent years,the overall survival of osteosarcoma patients has not been improved,obviously.Cancer cells preferentially use glycolysis instead of oxidative phosphorylation to meet their increased energetic and biosynthetic demands,a phenomenon known as the Warburg effect.Glycolysis is a driving factor in multiple cancers and is emerging as a new cancer target treatment.In the present study,we established a model to screen for glycolysis-associated genes in osteosarcoma.This risk score of the model were correlated with clinical characteristics osteosarcoma patients.Besides,a functional assay that identified STC2 enhanced glycolysis of osteosarcoma cells.Modulation of STC2 changes glucose consumption and lactate production as well as GLUT1 expression.Furthermore,we identified that change in the expression levels of STC2 affected the proliferation,invasion,and migration of osteosarcoma cells.Our finding identified STC2 as a new tumor-promoting factor of osteosarcoma cells through enhancing glycolysis.Method:1.GSEA enrichment was used to analyze the prognostic risk model of STC2 in patients with osteosarcoma;2.STC2 expression was detected by immunohistochemistry staining in normal and cancerous tissue samples;3.The proliferation,invasion,migration and apoptosis of osteosarcoma cells were examined after knockdown and overexpression of STC2;4.To investigate the effect of STC2 knockdown and overexpression on glycolysis pathway of osteosarcoma cells and its mechanism。Results:1.The enrichment of glycolytic metabolism and the screening of prognostic glycolysis-related genes in OS;2.The clinical prognostic value of glycolysis-related risk models;3.STC2 affects the proliferation,migration,invasion and apoptosis of osteosarcoma cells;4.STC2 promotes the glycolytic process in osteosarcoma cells by targeting GLUT1 and LDHA.Conclusion:STC2 is highly expressed in osteosarcoma tissues,and the prognostic model of STC2 was established to verify that STC2 promotes the development of osteosarcoma through glycolysis pathway and affects the growth,migration and invasion ability of osteosarcoma cells.STC2 is expected to become a new strategy for molecular targeted therapy of osteosarcoma.