Significance of miRNA in oncogenesis of soft part tumors.

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MicroRNAs (miRNA) are small non-coding RNAs whose aberrations are involved in the initiation and progression of human cancers. To seek unique miRNAs contributing to the development of osteosarcoma, we investigated the global miRNA expression profile. We focused on a commonly down-regulated miRNA, miR-127, and analyzed its relationship with the expression of its potential target, BCL6 protein. We found that 5 of 8 (63%) osteosarcoma cell lines exhibited marked down-regulation of miR-127 in comparison with the remaining cell lines and normal cultured osteoblasts. An inverse correlation between miR-127 and BCL6 protein expression was found in the osteosarcoma cell lines and primary-cultured normal osteoblasts. We demonstrated that overexpression of miR-127 induced a reduction of the BCL6 protein level, and confirmed target specificity between miR-127 and BCL6 by the luciferase reporter assay. Immunohistochemical analysis of BCL6 protein revealed that about half of the primary osteosarcomas (13/25, 52%) showed BCL6 overexpression, whereas normal osteoblasts were completely negative. The disease outcome of BCL6-positive patients was significantly worse than that of BCL6-negative patients (p<0.05). These results suggest that gain of BCL6 protein expression through the repression of miR-127 expression may be partly involved in osteosarcoma development.