title: MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis.
abstract: MicroRNAs (miRNAs) decrease the expression of specific target oncogenes or tumor suppressor genes and thereby play crucial roles in tumorigenesis and tumor growth. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. In this study, the miRNA microarray assay and hierarchical clustering analysis were performed in human osteosarcoma samples. In comparison with normal human skeletal muscle, 43 miRNAs were significantly differentially expressed in human osteosarcomas (fold change ≥2 and p≤0.05). Among these miRNAs, miR-133a and miR-133b expression was decreased by 135 folds and 47 folds respectively and the decreased expression was confirmed in both frozen and paraffin-embedded osteosarcoma samples. The miR-133b precursor expression vector was then transfected into osteosarcoma cell lines U2-OS and MG-63, and the stable transfectants were selected by puromycin. We found that stable over-expression of miR-133b in osteosarcoma cell lines U2-OS and MG-63 inhibited cell proliferation, invasion and migration, and induced apoptosis. Further, over-expression of miR-133b decreased the expression of predicted target genes BCL2L2, MCL-1, IGF1R and MET, as well as the expression of phospho-Akt and FAK. This study provides a new insight into miRNAs dysregulation in osteosarcoma, and indicates that miR-133b may play as a tumor suppressor gene in osteosarcoma.
authors.affiliation: Department of Medical Research, Liu Hua Qiao Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Huafu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic Surgery, Liu Hua Qiao Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Liu Hua Qiao Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Liu Hua Qiao Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, Liu Hua Qiao Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Guobo
authors.initials: G
authors.lastname: Lan
authors.affiliation: Department of Orthopedic Surgery, Liu Hua Qiao Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D015536:Down-Regulation; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; C579095:MCL1 protein, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D012334:RNA, Neoplasm; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D017526:Receptor, IGF Type 1; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt