title: Imatinib promotes apoptosis of giant cell tumor cells by targeting microRNA-30a-mediated runt-related transcription factor 2.
abstract: Giant cell tumor (GCT) is an aggressive type of bone tumor consisting of multinucleated osteoclast-like giant cells. Imatinib is a selective inhibitor for certain type III tyrosine kinase receptor family members with a variety of beneficial effects. The purpose of the present study was to determine the therapeutic potential and underlying mechanism of imatinib against GCT. In the present study, cell viability and apoptosis in GCT were analyzed using the MTT assay, flow cytometry and DAPI staining assay. Caspase-3 and -9 activity in GCT cells were analyzed with colorimetric assay kits. In addition, the expression levels of runt-related transcription factor 2 (RunX2) protein and microRNA-30a (miR-30a) in GCT cells were detected using western blotting and quantitative polymerase chain reaction, respectively. Results from the present study demonstrated that imatinib treatment inhibited cell viability, increased cell apoptosis, and significantly promoted caspase-3 and -9 activity in GCT. In addition, imatinib treatment decreased the RunX2 protein expression level. Notably, imatinib was demonstrated to increase miR-30a expression. However, upregulation of miR-30a expression reduced the RunX2 protein expression level, and downregulation of miR-30a expression reversed the anticancer effect of imatinib on GCT, increasing the expression level of RunX2 protein in GCT. The results of the present study indicate that imatinib promotes apoptosis of GCT cells by targeting the miR-30a-mediated RunX2 signaling pathway.
authors.affiliation: Department of Spinal Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Spinal Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Spinal Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Spinal Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Kuang
authors.affiliation: Department of Spinal Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005870:Giant Cell Tumors / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D014162:Transfection
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D000068877:Imatinib Mesylate; D053148:Caspase 3; D053453:Caspase 9