title: MiR-138 Acts as a Tumor Suppressor by Targeting EZH2 and Enhances Cisplatin-Induced Apoptosis in Osteosarcoma Cells.
abstract: Chemotherapeutic insensitivity remains a major obstacle to treating osteosarcoma effectively. Recently, increasing evidence has suggested that microRNAs (miRNAs) are involved in drug resistance. However, the effect of miR-138 on cisplatin chemoresistance in osteosarcoma has not been reported. We used real-time PCR to detect the expression of mature miR-138 in osteosarcoma tissues and cell lines. Cell proliferation, invasion, and migration assays were used to observe changes to the osteosarcoma malignant phenotype. MiR-138 was downregulated in osteosarcoma tissues and cell lines, and miR-138 overexpression negatively regulated osteosarcoma cell proliferation, migration, and invasion. We also verified that EZH2 is a direct target of miR-138. Furthermore, enhancing EZH2 expression reduced the inhibitory effects of miR-138 on osteosarcoma. Proliferation, apoptosis assays and caspase-3 activity assay confirmed that elevated miR-138 expression enhanced osteosarcoma cell chemosensitivity to cisplatin by targeting EZH2. In conclusion, the present study demonstrates that miR-138 acts as a tumor suppressor by enhancing osteosarcoma cell chemosensitivity and supports its potential application for treating osteosarcoma in the future.
authors.affiliation: Department of Orthopaedics, the Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, JiangSu Province, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, Affiliated Huai'an Hospital of Xuzhou Medical College, Huaian, JiangSu Province, China.
authors.forename: Jinshan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Orthopaedics, the Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, JiangSu Province, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, the Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, JiangSu Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Duan
authors.affiliation: Department of Orthopaedics, the Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, JiangSu Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Affiliated Huai'an Hospital of Xuzhou Medical College, Huaian, JiangSu Province, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000633:toxicity; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D053148:Caspase 3; D002945:Cisplatin