title: MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are a class of endogenously expressed, small noncoding RNAs, which suppress its target mRNAs at the post-transcriptional level. Studies have demonstrated that miR-34a, which is a direct target of the p53 tumor suppressor gene, functions as a tumor suppressor and is associated with the tumor growth and metastasis of various human malignances. However, the role of miR-34a in osteosarcoma has not been totally elucidated. In the present study, the effects of miR-34a on osteosarcoma and the possible mechanism by which miR-34a affected the tumor growth and metastasis of osteosarcoma were investigated.
  
  
  RESULTS
  Over-expression of miR-34a partially inhibited proliferation, migration and invasion of osteosarcoma cells in vitro, as well as the tumor growth and pulmonary metastasis of osteosarcoma cells in vivo. c-Met is a target of miR-34a, and regulates the migration and invasion of osteosarcoma cells. Osteosarcoma cells over-expressing miR-34a exhibited a significant decrease in the expression levels of c-Met mRNA and protein simultaneously. Finally, the results from bioinformatics analysis demonstrated that there were multiple putative targets of miR-34a that may be associated with the proliferation and metastasis of osteosarcoma, including factors in Wnt and Notch signaling pathways.
  
  
  CONCLUSIONS
  The results presented in this study demonstrated that over-expression of miR-34a could inhibit the tumor growth and metastasis of osteosarcoma probably through down regulating c-Met. And there are other putative miR-34a target genes beside c-Met which could potentially be key players in the development of osteosarcoma. Since pulmonary metastases are responsible for mortality of patient carrying osteosarcoma, miR-34a may prove to be a promising gene therapeutic agent. It will be interesting to further investigate the mechanism by which miR-34a functions as a tumor suppressor gene in osteosarcoma.
authors.affiliation: Department of Orthopedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Kang
authors.initials: K
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Tongtao
authors.initials: T
authors.lastname: Yang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Ma
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Qiu
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Fan
authors.forename: Baoan
authors.initials: B
authors.lastname: Ma
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000473:pathology*; D010957:Plasmids
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs