title: MicroRNA-124 suppresses the migration and invasion of osteosarcoma cells via targeting ROR2-mediated non-canonical Wnt signaling.
abstract: MicroRNAs (miRs) have been implicated in tumorigenesis through inhibition of the expression of their target genes at post-transcriptional levels. miR-124 has been found to be downregulated in many malignant tumors including osteosarcoma (OS). However, the detailed mechanism of miR-124 in the regulation of OS malignant phenotypes remains largely unclear. Here we aimed to explore the role of miR-124 in mediating OS cell migration and invasion, as well as the underlying regulatory mechanisms. Real-time RT-PCR data showed that miR-124 was frequently downregulated in OS cell lines compared to normal human osteoblast cells. We further conducted bioinformatic analysis and a luciferase reporter assay, and identified receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a novel target of miR-124. Furthermore, we found that ROR2 was significantly upregulated in OS cell lines compared to normal human osteoblast cells, and miR-124 negatively mediated the protein level of ROR2 in U-2OS and Saos-2 cells. Moreover, transfection with miR-124 mimics significantly suppressed migration and invasion in the U-2OS and Saos-2 cells, while overexpression of ROR2 in the miR-124-transfected OS cells reversed the inhibitory effect of miR-124 upregulation on OS cell migration and invasion. In addition, we found that overexpression of miR-124 significantly suppressed the activity of non-canonical Wnt signaling, downstream of ROR2. Based on these findings, we suggest that miR-124 may inhibit OS metastasis, partly at least, via targeting ROR2 and thus suppressing the activity of ROR2-mediated non-canonical Wnt signaling.
authors.affiliation: Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yihe
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics*; D060449:Wnt Signaling Pathway
chemical_list: D020413:3' Untranslated Regions; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors