Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Mol Cancer Ther. 2011 Aug;10(8):1337-45. doi: 10.1158/1535-7163.MCT-11-0096. Epub 2011 Jun 10.
microRNAs (miRNA, miR) play an important role in cancer cell growth and migration; however, the potential roles of miRNAs in osteosarcoma remain largely uncharacterized. By applying a miRNA microarray platform and unsupervised hierarchical clustering analysis, we found that several miRNAs have altered expression levels in osteosarcoma cell lines and tumor tissues when compared with normal human osteoblasts. Three miRNAs, miR-199a-3p, miR-127-3p, and miR-376c, were significantly decreased in osteosarcoma cell lines, whereas miR-151-3p and miR-191 were increased in osteosarcoma cell lines in comparison with osteoblasts. Transfection of precursor miR-199a-3p into osteosarcoma cell lines significantly decreased cell growth and migration, thus indicating that the inhibition effect is associated with an increase in the G(1)-phase and a decrease of the S-phase cell population. In addition, we observed decreased mTOR and Stat3 expression in miR-199a-3p transfected cells. This study provides new insights for miRNAs in osteosarcoma and suggests that miR-199a-3p may play a functional role in osteosarcoma cell growth and proliferation. Restoring miR-199a-3p's function may provide therapeutic benefits in osteosarcoma.
微小 RNA（miRNA，miR）在癌细胞生长和迁移中发挥重要作用；然而，miRNA 在骨肉瘤中的潜在作用在很大程度上仍未得到充分描述。通过应用 miRNA 微阵列平台和无监督层次聚类分析，我们发现与正常人类成骨细胞相比，几种 miRNA 在骨肉瘤细胞系和肿瘤组织中的表达水平发生了改变。与成骨细胞相比，miR-199a-3p、miR-127-3p 和 miR-376c 在骨肉瘤细胞系中显著下调，而 miR-151-3p 和 miR-191 在骨肉瘤细胞系中上调。将前体 miR-199a-3p 转染到骨肉瘤细胞系中可显著降低细胞生长和迁移，表明抑制作用与 G1 期细胞群增加和 S 期细胞群减少有关。此外，我们观察到 miR-199a-3p 转染细胞中 mTOR 和 Stat3 表达降低。本研究为骨肉瘤中的 miRNA 提供了新的见解，并表明 miR-199a-3p 可能在骨肉瘤细胞生长和增殖中发挥功能作用。恢复 miR-199a-3p 的功能可能为骨肉瘤提供治疗益处。
