MicroRNA-138 functions as a tumor suppressor in osteosarcoma by targeting differentiated embryonic chondrocyte gene 2

Background: microrna-138 (mir-138) has been proven to be a tumor suppressor gene in various types of tumors. however,the expression and the role of mir-138 in human osteosarcoma are still poorly understood. we investigated the function and the underlying mechanism of mir-138 in osteosarcoma. methods: the expression of mir-138 in human osteosarcoma tissues and cell lines was detected by real-time pcr analysis. the gain-of-function and loss-of-function experiments were performed on osteosarcoma cell lines to investigate the effects of mir-138 on osteosarcoma progression,and to determine whether differentiated embryonic chondrocyte gene 2 (dec2) mediates these effects. cell proliferation,apoptosis and invasion were assessed by mtt,flow cytometry and transwell-matrigel assays. dual-luciferase reporter assay was used to identify whether dec2 is a direct target of mir-138. results: mir-138 was significantly downregulated in human osteosarcoma tissues and cell lines. moreover,mir-138 expression was significantly lower in metastatic osteosarcoma tissues than that in non-metastatic tissues. the in vitro gain-of-function and loss-of-function experiments demonstrated that mir-138 inhibited cell proliferation and invasion,and promoted cell apoptosis of human osteosarcoma cells. dec2 was verified as a direct target of mir-138,and dec2 could reverse the inhibitory effect of mir-138 on osteosarcoma progression. conclusions: these findings suggested that mir-138 acts as a tumor suppressor in osteosarcoma.mir-138 inhibited cell proliferation and invasion,as well as promoted cell apoptosis of human osteosarcoma cells,at least partially,by inhibiting the expression of dec2. mir-138/dec2 may be a novel therapeutic target in osteosarcoma. © 2016 jiang et al.