MicroRNA-206 Regulates Proliferation,Migration And Invasion Of Ewing’s Sarcoma Cells By Targeting KHSRP

Ewing’s sarcoma(ES),characterized by small round cells,is the second most common primary malignant bone tumor children and adolescents with rapid progression and aggressive metastatic potential.Although great efforts has been exerted in diagnosis and therapeutic treatment over the past decades,including adjuvant chemotherapy,radiation and surgery,the prognosis of ES remains poor as 5 year disease-free survival rate is below 70% and 30% in localized and metastatic patients,respectively.Thus,better understanding of the underlying ES carcinogenesis is critical to develop novel diagnostic and therapeutic targets for the clinical strategies.Accumulating evidence indicated that aberrant microRNAs acted as oncogenes and suppressors in the pathogenesis of tumor progression and were up-/down-regulated in a variety of tumors including ES.Emerging evidence suggested that microRNA-206 played an inhibitory role in many human cancers.microRNA-206 prohibited cell proliferation and cell cycle of renal cancer cell by targeting cell division kinase CDK9 and CDK4.microRNA-206 was confirmed to be an inhibitor of tumorigenesis in colon carcinoma cells by targeting d-MET.Moreover,other results showed that microRNA-206 repressed the migration of breast cancer by targeting VEGFA,reduced the proliferation,colony formation,migration,invasion of osteosarcoma via targeting ANXA2 and inhibited liver cancer by targeting notch3.However,previous studies focusing on the role of microRNA-206 in ES remains largely unknown.Our study showed that microRNA-206 was significantly down-regulated in ES tissues and correlated with poor survival rate of patients.Furthermore,cell functional experiments demonstrated that the overexpression of microRNA-206 prohibited ES cell proliferation,migration and invasion.All these results confirmed that microRNA-206 plays an inhibitory role in ES development.Here,we firstly demonstrated that microRNA-206 suppressed KHSRP expression by directly binding to the 3’UTR of KHSRP.Furthermore,microRNA-206 revealed an inverse correlation with KHSRP expression in ES tissues.KHSRP knockdown prohibited the ES cell proliferation,migration and invasion.Thus these results demonstrated the critical role of KHSRP in tumor progression of ES cells regulated by microRNA-206.Moreover,KHSRP restoration could reverse the cell functional effects of microRNA-206 overexpression on the proliferation,migration and invasion of ES cells.Taken together,these findings may provide a novel insight into microRNA-206/KHSRP axis in ES.Recently,we found the expression of microRNA-206 decreased in ES cells and tissues.The down-regulated expression was confirmed to be correlated with poor prognosis.Functional experiments indicated that microRNA-206 overexpression suppressed ES cell proliferation,migration and invasion.In vitro mechanistic studies demonstrated that microRNA-206 repressed ES progression by targeting KHSRP.Taken together,our results indicated a novel microRNA-206-KHSRP axis in ES.In summary,our findings revealed that microRNA-206 was decreasingly expressed both in ES tissues and cells.Its downregulation correlated with pernicious clinical features,which we may predict the poor survival rate of patients based on it.Moreover,through binding directly to the 3’UTR of KHSRP,microRNA-206 prohibited ES cell proliferation,migration and invasion.In general,our results provide a novel prospective on the molecular targets for ES,however,the exact underling mechanism of how microRNA-206 and KHSRP represses ES is still not fully understood,and will be addressed in the future study.