title: MicroRNA-224 promotes the sensitivity of osteosarcoma cells to cisplatin by targeting Rac1.
abstract: Osteosarcoma is the most common primary bone tumour in children and adolescents. Accumulating evidence has shown that microRNAs (miRNAs) participate in the development of almost all types of cancer. Here, we investigated the role of miR-224 in the development and progression of osteosarcoma. We demonstrated that miR-224 was down-regulated in osteosarcoma cell lines and tissues. Lower miR-224 levels were correlated with shorter survivalin osteosarcoma patients. Furthermore, overexpression of miR-224 suppressed osteosarcoma cell proliferation, migration and invasion and contributed to the increased sensitivity of MG-63 cells to cisplatin. We identified Rac1 as a direct target gene of miR-224 in osteosarcoma. Rac1 expression was up-regulated in the osteosarcoma cell lines and tissues, and there was an inverse correlation between Rac1 and miR-224 expression in osteosarcoma tissues. Furthermore, rescuing Rac1 expression decreased the sensitivity of miR-224-overexpressing MG-63 cells to cisplatin. We also demonstrated that ectopic expression of Rac1 promoted the proliferation, migration and invasion of miR-224-overexpressing MG-63 cells. These data suggest that miR-224 plays a tumour suppressor role in the development of osteosarcoma and is related to the sensitivity of osteosarcoma to cisplatin.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Prov., China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Prov., China.
authors.forename: Lina
authors.initials: L
authors.lastname: Gu
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Sir James Spence Institute, RVI Hospital, UK.
authors.forename: Fang
authors.initials: F
authors.lastname: Ju
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Prov., China.
authors.forename: Hepeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Prov., China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Prov., China.
authors.forename: Han
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Prov., China.
authors.forename: ZhengGang
authors.initials: Z
authors.lastname: Bi
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Prov., China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D020830:rac1 GTP-Binding Protein; D002945:Cisplatin
keywords: Rac1; cisplatin; miR-224; microRNA; osteosarcoma