title: miR-382 inhibits osteosarcoma metastasis and relapse by targeting Y box-binding protein 1.
abstract: Lung metastasis and relapse in osteosarcoma (OS) patients indicate poor prognosis. Here, we identified significantly decreased expression of miR-382 in highly metastatic OS cell lines and relapsed OS samples compared to their parental cell lines and primary OS samples, respectively. In addition, our clinical data showed that the miR-382 expression level was inversely associated with relapse and positively associated with metastasis-free survival in OS patients. The overexpression of miR-382 suppressed epithelial-mesenchymal transition (EMT) and metastasis. This overexpression also decreased the cancer stem cell (CSC) population and function in OS cells. In contrast, inhibition of miR-382 stimulated EMT and metastasis and increased CSC population in OS cells. In addition, our in vivo experiments showed that the overexpression of miR-382 inhibited CSC-induced tumor formation, and the combination of miR-382 with doxorubicin prevented disease relapse in OS patients. Furthermore, we demonstrated that miR-382 exerted its tumor-suppressing potential by directly targeting Y box-binding protein 1 (YB-1) in OS. Taken together, our findings suggest that miR-382 functions as a tumor suppressor function and that the overexpression of miR-382 is a novel strategy to inhibit tumor metastasis and prevent CSC-induced relapse in OS.
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.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Cheng-Xiong
authors.initials: CX
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pathology, The General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Song
authors.affiliation: Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Bi
authors.affiliation: Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001483:Base Sequence; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays; D051840:Y-Box-Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C555413:MIRN382 microRNA, human; D035683:MicroRNAs; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D004317:Doxorubicin