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.
Highlights
Osteosarcoma (OS) is an aggressive bone tumor characterized by malignant osteoid production and osteoblastic differentiation
To confirm the results of miRNA microarray assay, SYBR Green quantitative real-time PCR (qRT-PCR) was performed using the RNAs from five human osteosarcoma and three normal muscle samples in miRNA microarray assay as templates
We found that miR-133a, miR133b and miR-208b expressions significantly decreased in osteosarcomas (p#0.01) while miR-645 expression significantly increased (p#0.01) (Figure 2)
Summary
Osteosarcoma (OS) is an aggressive bone tumor characterized by malignant osteoid production and osteoblastic differentiation. It is an infrequent but the most common and destructive primary bone tumor in children and adolescent. By binding to the complementary target mRNA, miRNAs lead to mRNA degradation or preventing mRNA from being translated. MiRNAs regulate target genes expression at post-transcriptional level. Over-expression of miRNAs usually gives rise to the deceased expression of target genes. Evidence showes that 98 miRNAs locate at fragile sites and genomic regions involved in cancer, indicating that miRNAs are tightly interrelated with tumorigenesis and tumor progression [4]. By mediating the expression of oncogenes or tumor suppressors, miRNAs play a critical role in tumor growth, progression, metastasis, and drug resistance [5,6]
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