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Objectives: To explore the biological function of miR-381 in OS. Materials and Methods: Immunohistochemistry or in-situ hybridization (ISH) was performed to detect miR-381 or LRRC4 status. MiR-381 mimics or miR-381 antago was transfected into MG-63 cells to regulated miR-381. qRT-PCR was used to analyze the expression level of genes in MG-63 transfected genes or treated with drugs. And western blotting was used to analyze the expression level of proteins.The target of miR-381 was predicted by TargetScan and confirmed by luciferase reporter assay. Cell proliferation was analysis by CCK-8 and The 5-ethynyl-2-deoxyuridine (Edu) incorporation assay. Transwell/Matrigel invasion assay to shown the MG-63 invasion. Chemotherapy sensitivity of MG-63 was also analysis by CCK-8.