title: Epirubicin-mediated expression of miR-302b is involved in osteosarcoma apoptosis and cell cycle regulation.
abstract: Epirubicin is widely used in osteosarcoma chemotherapy. Growing evidence indicates that the microRNA (miRNA) expression levels which are induced by chemotherapeutic agents play an important role in osteosarcoma development and progression. In this study we investigate the alterations of miRNA expression in the osteosarcoma cells after epirubicin treatment and whether miRNAs can enhance its anti-osteosarcoma effect. After epirubicin exposure, microarray shows 40 miRNAs are differentially expressed in osteosarcoma cells including 24 down-regulated miRNAs. Notably, miR-302b, which is stably low-expressed in osteosarcoma, could be induced by the epirubicin. Furthermore, we find that miR-302b can inhibit the osteosarcoma cell proliferation, promote cell apoptosis and cell cycle arrest MiR-302b can activate caspase-3 and regulate the Akt/pAkt, Bcl-2, Bim expression to increase the cell apoptosis. Meanwhile, miR-302b also attenuates cyclin D1 and CDKs expression to induce cell cycle arrest. Therefore, our results suggest miR-302b can play an essential role in osteosarcoma treatment as a potential tumor suppressor.
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Lu
authors.initials: L
authors.lastname: Song
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Renxiong
authors.initials: R
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000096:biosynthesis; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis; D015251:Epirubicin / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000903:Antibiotics, Antineoplastic; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; D015251:Epirubicin; D012313:RNA; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D053148:Caspase 3
keywords: Epirubicin; Microrna; Mirna-302b; Osteosarcoma