title: Inhibition of Src by microRNA-23b increases the cisplatin sensitivity of chondrosarcoma cells.
abstract: Chondrosarcomas are malignant cartilage-forming tumors from low-grade to high-grade aggressive tumors characterized by metastasis. Cisplatin is an effective DNA-damaging anti-tumor agent for the treatment against a wide variety of solid tumors. However, chondrosarcomas are notorious for their resistance to conventional chemo- and radio- therapies. In this study, we report miR-23b acts as a tumor suppressor in chondrosarcoma. The expressions of miR-23b are down-regulated in chondrosarcoma patient samples and cell lines compared with adjacent normal tissues and human primary chondrocytes. In addition, overexpression of miR-23b suppresses chondrosarcoma cell proliferation. By comparison of the cisplatin resistant chondrosarcoma cells and parental cells, we observed miR-23b was significantly down regulated in cisplatin resistant cells. Moreover, we demonstrate here Src kinase is a direct target of miR-23b in chondrosarcoma cells. Overexpression of miR-23b suppresses Src-Akt pathway, leading to the sensitization of cisplatin resistant chondrosarcoma cells to cisplatin. This chemo-sensitivity effect by the miR-23b-mediated inhibition of Src-Akt pathway is verified with the restoration of Src kinase in miR-23b-overespressing chondrosarcoma cells, resulting in the acquirement of resistance to cisplatin. In summary, our study reveals a novel role of miR-23b in cisplatin resistance in chondrosarcoma and will contribute to the development of the microRNA-targeted anti-cancer therapeutics.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Mo-Song
authors.initials: MS
authors.lastname: Yang
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Tang
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000235:genetics* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016391:Genes, src; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin
keywords: Src-Akt pathway; cancer therapeutics; chondrosarcoma cells; microRNA-23b