title: MiR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1.
abstract: Although the 5-year survival rate of osteosarcoma (OS) has risen to ~60-70%, a substantial portion of patients still respond poorly to chemotherapy and have a high risk of relapse or metastasis even after curative resection. In this study, we found that the expression of miR-142 was significantly reduced in OS tissues and OS cell lines, while Ras-related C3 botulinum toxin substrate 1 (Rac1) expression was increased in the OS tissues and OS cell lines compared with expression in the controls. We then demonstrated that miR-142 regulated Rac1 expression at the transcriptional and translational levels by directly targeting its 3'-untranslated region (3'UTR). In addition, by loss- and gain-of function experiments, we investigated the role of miR-142 in OS cell lines and found that miR-142 acted as a tumor suppressor in the OS cell lines and inhibited cell proliferation and cell invasion and arrested cell cycle in the S phase. Furthermore, miR-142 inhibited osteosarcoma cell invasion by inducing E-cadherin expression and reducing expression of matrix metalloproteinase 2 (MMP2) and MMP9. Thus, overexpression of miR-142 and/or knockdown of Rac1 would be a novel target for OS therapy in the future.
authors.affiliation: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Muliang
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jiangdong
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Deye
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D020830:rac1 GTP-Binding Protein