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ARTICLE
MicroRNA-33b Inhibits the Proliferation and Migration of Osteosarcoma Cells via Targeting Hypoxia-Inducible Factor-1α
Department of Second Orthopedics, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China
Oncology Research 2017, 25(3), 397-405. https://doi.org/10.3727/096504016X14743337535446
Abstract
Recently, microRNA (miR)-33b has been demonstrated to act as a tumor suppressor in osteosarcoma. However, the regulatory mechanism of miR-33b in osteosarcoma cell proliferation and migration remains largely unknown. In this study, real-time PCR showed that miR-33b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Its expression was also decreased in several common osteosarcoma cell lines, including Saos-2, MG63, U2OS, and SW1353, when compared to normal osteoblast cell line hFOB. Overexpression of miR-33b suppressed U2OS cell proliferation and migration. HIF-1α was further identified as a target of miR-33b, and its protein levels were reduced after overexpression of miR- 33b in U2OS cells. Moreover, overexpression of HIF-1α significantly reversed the suppressive effect of miR- 33b on U2OS cell proliferation and migration. In addition, HIF-1α was found to be significantly upregulated in osteosarcoma tissues compared to adjacent nontumor tissues, and their expression levels were inversely correlated to the miR-33b levels in osteosarcoma tissues. According to these findings, miR-33b plays a suppressive role in the regulation of osteosarcoma cell proliferation and migration via directly targeting HIF-1α. Therefore, we suggest that the miR-33b/HIF-1α axis may become a promising therapeutic target for osteosarcoma.Keywords
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