title: The tumor suppressor miR-124 inhibits cell proliferation and invasion by targeting B7-H3 in osteosarcoma.
abstract: Our previous studies have shown that the expression level of B7 homolog 3 (B7-H3) was correlated with clinical staging and prognosis of osteosarcoma (OS) patients, and its silencing inhibited the proliferation and invasion of OS cells in vitro. However, its overexpression mechanism behind was far from elucidated. On the basis of bioinformatics and the preliminary screening data, we hypothesized that miR-124 might play an important role in OS development and as a lead candidate for modulating B7-H3 expression. In this study, we found that miR-124 was downregulated significantly in OS tumor tissue, compared to normal adjacent tissues (NATs). Lower miR-124 expression levels were associated with advanced Ennecking stage, lower tumor differentiation, and common pulmonary metastasis. The 5-year overall survival rate in the miR-124 upregulated group was 61.5 %, while with low miR-124 expression, only 11.8 % survived. Further studies in vitro showed that B7-H3 was a direct target of miR-124. Overexpression of miR-124 decreased B7-H3 mRNA and protein level and inhibited B7-H3 3'-UTR reporter activity. Treatment of OS cells with miR-124 mimics induced the inhibition of cell growth and invasion in vitro, which could be abrogated by transfected by B7-H3 expression vector. Our findings highlight the potential application of miR-124 as a novel onco-miRNA in OS, and its oncogenic effects are mediated chiefly through downregulation of B7-H3, thus suggesting a model for identifying miR-124 that can be exploited to improve the therapeutic potential efficacy of mAb targeting to B7-H3.
authors.affiliation: Cancer Research Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.|Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Liver Diseases, Bethune International Peace Hospital, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Fu-Biao
authors.initials: FB
authors.lastname: Kang
authors.affiliation: Blood transfusion division, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Liver Diseases, Bethune International Peace Hospital, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Cancer Research Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China. shanbaoen_1962@163.com.
authors.forename: Bao-En
authors.initials: BE
authors.lastname: Shan
mesh_terms: D000328:Adult; D060887:B7 Antigens / Q000096:biosynthesis* / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D055815:Young Adult
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human; C509207:MIRN124 microRNA, human; D035683:MicroRNAs
keywords: B7-H3; Invasion; Osteosarcoma; Proliferation; miR-124