title: MiR-34c inhibits osteosarcoma metastasis and chemoresistance.
abstract: Studies have shown that miR-34c is associated with metastasis and the chemoresponse of several cancers, but its role in osteosarcoma (OS) is unclear. Here, we investigated the role and mechanism of miR-34c in OS metastasis and chemoresponse. In this study, we found that the expression of miR-34c was significantly decreased in specimens from OS patients with a poor chemoresponse or metastasis compared to those with a good chemoresponse and no metastasis. The inhibition of miR-34c significantly stimulated OS cell invasion and chemoresistance in vitro. In contrast, restoring miR-34c significantly inhibited OS cell invasion and chemoresistance. Furthermore, we identified Notch1 and lymphoid enhancer-binding factor 1 (LEF1) as target genes of miR-34c in OS cells and demonstrated that Notch1 and LEF1 have a major role in the effects of miR-34c on OS cell chemosensitivity and metastasis. Taken together, our data indicate that miR-34c suppresses OS metastasis and chemoresistance by targeting Notch1 and LEF1. Restoring miR-34c may have important implications for the development of strategies for inhibiting metastasis and overcoming OS cell resistance to chemotherapy.
authors.affiliation: Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Cheng-Xiong
authors.initials: CX
authors.lastname: Xu
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Bi
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D004317:Doxorubicin; D002945:Cisplatin