miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3

There is accumulating evidence that microRNAs are involved in multiple processes in development and tumor progression. Abnormally expressed miR-125b was found to play a fundamental role in several types of cancer; however, whether miR-125b participates in regulating the initiation and progress of osteosarcoma still remains unclear. Here we demonstrate that miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. The ectopic restoration of miR-125b expression in human osteosarcoma cells suppresses proliferation and migration in vitro and inhibits tumor formation in vivo. We further identified signal transducer and activator of transcription 3 (STAT3) as the direct and functional downstream target of miR-125b. Interestingly, we discovered that the expression of miR-125b is regulated by STAT3 at the level of transcription. STAT3 binds to the promoter region of miR-125b in vitro and serves as a transactivator. Taken together, our findings point to an important role in the molecular etiology of osteosarcoma and suggest that miR-125b is a potential target in the treatment of osteosarcoma.

► miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines.
► Ectopic restoration of miR-125b suppresses cell proliferation and migration in vitro.
► STAT3 is the direct and functional downstream target of miR-125b.
► STAT3 can bind to the promoter region of miR-125b and serves as a transactivator.