The Long Non-coding RNA WAC-AS1 Promotes Progression And Cancer Stemness Features In Osteosarcoma Via MiR-373-3p

Introduction: Osteosarcoma(OS)is one of the most common primary bone malignancies that seriously threaten the life and health of adolescents.Cancer stem cells(CSC)are a small subset of cancer cells,which have the ability to self-renew and sustain the tumor.The persistence of CSCs is the main cause of tumor recurrence and metastasis.Osteosarcoma is considered as a dedifferentiated disease caused by genetic and epigenetic changes that block the process by which osteoblasts differentiate from Mesenchymal stem cell.Long non-codingRNA(LncRNA)has been discovered with biological function in recent years.Its length is between 200 and 10000 nt,and it has several functions to control gene expression.LncRNA WAC-AS1 is highly expressed in most tumor cells,while the roles of WAC-AS1 in osteosarcoma are unknown.The aim of this study was to investigate the effects of WAC-AS1 in OS cells and CSC.Materials & Methods: The proliferation ability was examined by CCK8 assay and colony formation assay when WAC-AS1 overexpression or knockdown.The migration and invasion of cells were monitored by wound-healing assay and transwell cell assay,respectively.The apoptosis was monitored by flow cytometry(C6,BD Biosciences).The expression of lncRNA WAC-AS1 in cancer cell and CSC was monitored by real-time PCR.The self-renewing capabilities of the cells were assessed by spheroid formation assay.The localization of WAC-AS1 was detected by in situ immunofluorescence hybridizationResults: Over-expression of WAC-AS1 promoted cell proliferation,migration and invasion,while promoted reduce OS apoptosis.The same results were found when knockdown of WAC-AS1.WAC-AS1 regulated the malignant behavior of OS by modulating to mi R-373-3p,which functions as a tumor suppressor.In addition,Over-expression of WAC-AS promoted stemness feature and expression of CD133.WAC-AS1 is localized in the cytoplasm and may influence the progression of osteosarcoma by regulating the function of mi R-373-3p.Conclusion:(1)the high expression of WAC-AS1 in tumor tissue promotes the progress of Osteosarcoma;(2)WAC-AS1 promotes the self-renewal of Osteosarcoma and reduces the drug sensitivity of cisplatin and Adriamycin;(3)WAC-AS1 may regulate the development of osteosarcoma through MIR-373-3P.