title: MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1.
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.
authors.affiliation: Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: C570046:MIRN340 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases
keywords: Osteosarcoma; ROCK1; miR-340