[No authors listed]
Emerging evidence has indicated that microRNAs (miRs) are involved in the malignant behavior of cancer. The present study explored the role of miRâ193b 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 miRâ193b. Furthermore, miRâ193b exerted negative effects on cell proliferation, colony formation, cell cycle progression, migration and invasion, and induced apoptosis. In vivo studies revealed negative influences of miRâ193b on tumorigenesis and metastasis. The tumorâsuppressive role of miRâ193b was achieved by targeting KRAS and stathmin 1 (STMN1). Notably, overexpression of KRAS and STMN1 attenuated the miRâ193bâinduced inhibition of malignant behaviors. There was a doubleânegative regulatory loop between MYC and miRâ193b, with MYC inhibiting miRâ193b expression by directly binding to its promoter region and miRâ193b negatively influencing MYC expression indirectly through some unknown mechanism. Collectively, these findings indicated that miRâ193b may serve a tumor suppressive role in osteosarcoma by targeting KRAS and STMN1. The doubleânegative regulatory loop between MYC and miRâ193b may contribute to the sustained upregulation of MYC, the downregulation of miRâ193b, and to the subsequently enhanced expression of KRAS and STMN1, which may eventually lead to the development and metastasis of osteosarcoma.
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