LAUSR

Emerging evidence has indicated that microRNAs (miRs) are involved in the malignant behavior of cancer. The present study explored the role of miR-193b in the development and metastasis of osteosarcoma. Compared with F4 osteosarcoma cells, which have a relatively low metastatic potential, highly metastatic F5M2 cells exhibited a lower expression of miR-193b. Furthermore, miR-193b exerted negative effects on cell proliferation, colony formation, cell cycle progression, migration and invasion, and induced apoptosis. In vivo studies revealed negative influences of miR-193b on tumorigenesis and metastasis. The tumor-suppressive role of miR-193b was achieved by targeting KRAS and stathmin 1 (STMN1). Notably, overexpression of KRAS and STMN1 attenuated the miR-193b-induced inhibition of malignant behaviors. There was a double-negative regulatory loop between MYC and miR-193b, with MYC inhibiting miR-193b expression by directly binding to its promoter region and miR-193b negatively influencing MYC expression indirectly through some unknown mechanism. Collectively, these findings indicated that miR-193b may serve a tumor suppressive role in osteosarcoma by targeting KRAS and STMN1. The double-negative regulatory loop between MYC and miR-193b may contribute to the sustained upregulation of MYC, the downregulation of miR-193b, and to the subsequently enhanced expression of KRAS and STMN1, which may eventually lead to the development and metastasis of osteosarcoma.