miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

Osteosarcoma has become one of the most common primary malignant tumors affecting children and adolescents. Although increasing evidence has indicated that microRNAs (miRNAs or miRs) play important roles in the development of osteosarcoma, the expression of miR-27a-3p and its effects on osteosarcoma are not yet fully understood. In the present study, our data demonstrated that the expression of miR-27a-3p in osteosarcoma cell lines was significantly higher than that in the normal human osteoblastic cell line, hFOB 1.19 cell (P<0.01). In order to explore the role of miR-27a-3p in the development and progression of osteosarcoma, the expression of miR-27a-3p was inhibited by transfection of the MG-63 cells with miR-27a-3p inhibitor. The results revealed that the cell proliferative ability significantly decreased (P<0.01), the number of apoptotic cells significantly increased (P<0.01) and the number of cells passing through the Transwell membrane was significantly reduced in the group transfected with the miR-27a-3p inhibitor (P<0.01). At the same time, the expression of E-cadherin and -catenin was significantly upregulated (P<0.01), while the expression of vimentin was significantly downregulated in the group transfected with the miR-27a-3p inhibitor (P<0.01). Our results also revealed that the mRNA expression of ten-eleven translocation 1 (TET1) in the osteosarcoma cells was significantly downregulated compared with that in the hFOB 1.19 cells (P<0.01). Luciferase reporter system analysis indicated that miR-27a-3p recognized the TET1 3-UTR. The protein expression of TET1 significantly increased in the group transfected with the miR-27a-3p inhibitor. The results from CCK-8 assay, flow cytometric assay and Transwell invasion analysis revealed that TET1 knockdown inhibited the biological effects induced by the downregulation of miR-27a-3p. Taken together, the findings of this study indicate that miR-27a-3p is upregulated, while TET1 is downregulated in human osteosarcoma cells. miR-27a-3p inhibition suppresses the proliferation and invasion of osteosarcoma cells, and promotes cell apoptosis via the negative regulation of TET1. miR-27a-3p/TET1 may thus be a potential target for the treatment of osteosarcoma.