title: MicroRNA-205 acts as a tumor suppressor in osteosarcoma via targeting RUNX2.
abstract: MicroRNAs (miRs) are a class of small non-coding RNAs, and negatively regulate gene expression through directly binding to the 3'-untranslational region (UTR) of their target mRNA, which further leads to translational repression or mRNA degradation. Recently, various miRs have been implicated in the development and progression of osteosarcoma (OS). However, the underlying mechanism has not been fully uncovered. Our study aimed to reveal the exact role of miR-205 in OS, as well as the regulatory mechanism. In this study, we found that the expression of miR-205 was significantly reduced in a total of 34 OS tissue specimens compared to their matched adjacent normal tissues. Besides, it was also remarkably downregulated in OS cell lines (Saos-2, U2OS, SW1353, and MG63) compared to human osteoblast hFOB1.19 cells. Overexpression of miR-205 caused a significant decrease in the proliferation, migration and invasion of MG63 and U2OS cells. Runt-related transcription factor 2 (RUNX2) was further identified as a target gene of miR-205. Moreover, the mRNA and protein expression of RUNX2 was reduced after miR-205 overexpression, but increased after knockdown of miR-205 in MG63 and U2OS cells. Furthermore, overexpression of RUNX2 effectively reversed the suppressive effect of miR-205 on the proliferation, migration, and invasion of MG63 and U2OS cells. The RUNX2 level was significantly increased in OS tissues compared to their matched adjacent normal tissues, as well as in OS cell lines compared to hFOB1.19 cells. In addition, the RUNX2 level was reversely correlated with the miR-205 level in OS tissues. Taken together, our data demonstrate that miR-205 acts as a tumor suppressor in OS via directly targeting RUNX2. Therefore, we suggest that the miR-205/RUNX2 axis may serve as a potential target for the treatment of OS.
authors.affiliation: Department of Orthopaedics, Xiangya Hospital, 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, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Long
authors.affiliation: Department of Orthopaedics, Xiangya Hospital, 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, 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, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; D050659:Core Binding Factor Alpha 1 Subunit; D035683:MicroRNAs; C534425:MIR205, human; C493709:RUNX2 protein, human