title: Mir-664 promotes osteosarcoma cells proliferation via downregulating of FOXO4.
abstract: BACKGROUND
  Uncontrol cell growth and proliferation is acknowledged to responsible for cancer-related deaths by disorganizing the balance of growth promotion and growth limitation. Aberrant expression of microRNA play essential roles in cancer development, leads to cell proliferation, growth and survival, and promotes the development of various human tumors, including osteosarcoma. Elucidating the molecular mechanism of this abnormality in osteosarcoma carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy.
  
  
  METHODS
  The expression of miR-664 in osteosarcoma cell lines and osteosarcoma tissues was examined using real-time PCR. The effects of miR-664 on osteosarcoma cell proliferation were evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, colony formation and Anchorage-independent growth ability assay. The effect of miR-664 on FOXO4 was determine by luciferase assays and western blot assay.
  
  
  RESULTS
  The expression of miR-664 was markedly upregulated in osteosarcoma cell lines and tissues, and upregulation of miR-664 enhanced, whereas downregulation of miR-664 inhibited the proliferation of osteosarcoma cells in vivo. Furthermore, using bioinformatics and biological approaches, we showed that miR-664 directly targeted and suppressed the expression of tumor suppressors FOXO4.
  
  
  CONCLUSIONS
  Our findings suggest that miR-664 functions as an oncogene miRNA and has an important role in promoting human osteosarcoma cell proliferation by suppressing FOXO4 expression. These data suggests that miR-664 may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in osteosarcoma.
authors.affiliation: Department of Orthopedic Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangdong Province, Guangzhou 510515, China; Department of Orthopedic Spinal Surgery, Chenzhou NO.1 People's Hospital, HuNan Province, Chenzhou 0735, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangdong Province, Guangzhou 510515, China; Department of Orthopedic Spinal Surgery, Yue Bei People's Hospital Guangdong Province, Yuebei, 0751 China.
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Orthopedic Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangdong Province, Guangzhou 510515, China; Department of Orthopedic Spinal Surgery, The 2th affiliated hospital of University of South of China, HuNan Province, Hengyang 0734, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chenzhou NO.1 People's Hospital, HuNan Province, Chenzhou 0735, China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Orthopedic Spinal Surgery, Chenzhou NO.1 People's Hospital, HuNan Province, Chenzhou 0735, China.
authors.forename: Sheting
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Spinal Surgery, Chenzhou NO.1 People's Hospital, HuNan Province, Chenzhou 0735, China.
authors.forename: Zuozhong
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Orthopedic Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangdong Province, Guangzhou 510515, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Orthopedic Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangdong Province, Guangzhou 510515, China. Electronic address: Chenjt99@tom.com.
authors.forename: Jianting
authors.initials: J
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D051858:Forkhead Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; C000590115:MIRN664 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors
keywords: FOXO4; MiR-664; Osteosarcoma; Proliferation