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Biochem Biophys Res Commun. 2013 Aug 9;437(4):653-8. doi: 10.1016/j.bbrc.2013.07.033. Epub 2013 Jul 18.

MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1.

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1
Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, China.

Abstract

MicroRNAs (miRNAs) play key roles in cancer development and progression. In the present study, we investigated the role of miR-340 in the progression and metastasis of osteosarcoma (OS). Our results showed that miR-340 was frequently downregulated in OS tumors and cell lines. Overexpression of miR-340 in OS cell lines significantly inhibited cell proliferation, migration, and invasion in vitro, and tumor growth and metastasis in a xenograft mouse model. ROCK1 was identified as a target of miR-340, and ectopic expression of miR-340 downregulated ROCK1 by direct binding to its 3' untranslated region. siRNA-mediated silencing of ROCK1 phenocopied the effects of miR-340 overexpression, whereas restoration of ROCK1 in miR-340-overexpressing OS cells reversed the suppressive effects of miR-340. Together, these findings indicate that miR-340 acts as a tumor suppressor and its downregulation in tumor tissues may contribute to the progression and metastasis of OS through a mechanism involving ROCK1, suggesting miR-340 as a potential new diagnostic and therapeutic target for the treatment of OS.

KEYWORDS:

Osteosarcoma; ROCK1; miR-340

PMID:
23872151
DOI:
10.1016/j.bbrc.2013.07.033
[Indexed for MEDLINE]
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