MiR-125b suppresses the carcinogenesis of osteosarcoma cells via the MAPK-STAT3 pathway.

The microRNA (miRNA) miR-125b is abnormally expressed in many different types of tumors, including osteosarcoma (OS). How aberrantly expressed miR-125b participates in regulating the initiation and progression of OS is still poorly understood. In the current study, we found that in OS, miR-125b can suppress the expression of MAP kinase kinase 7 (MKK7), which can dephosphorylate and inactivate signal transducer and activator of transcription 3 (STAT3). We also identified an elevated expression level of MKK7 in OS and an association between MKK7 expression and poor prognosis. Further, miR-125b inhibited OS cell proliferation and invasion by targeting and downregulating MKK7 in vitro and suppressed tumor formation in vivo. Moreover, using Western blot analysis, we preliminarily proved that the activation (phosphorylation) of STAT3 was regulated by MKK7 at the epigenetic level. MKK7 was overexpressed in OS and associated with poor clinical results. The miR-125b-MAPK-STAT3 axis may be one of the mechanisms of OS oncogenesis and a potential target for the treatment of OS.