Department of Orthopaedic Surgery, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing, PR China.
Biomed Pharmacother. 2013 Jun;67(5):381-6. doi: 10.1016/j.biopha.2013.03.013. Epub 2013 Apr 3.
Osteosarcoma is one of the most common tumors. The mechanisms of formation and development of osteosarcoma have been studied for a long time. Recently, more and more evidence showed that miRNAs play important roles in regulating tumor growth. In this study we found that miRNA-223 was downregulated in both osteosarcoma patients' tumor tissues and osteosarcoma cell lines. Overexpression of miRNA-233 greatly inhibited the proliferation of Saos-2 cells. Cell cycle analysis by flow cytometry showed the arrest of cell cycle progression at the G1 phase. Further mechanistic study indicated that Ect2 was directly targeted by miR-223. Downregulation of Ect2 by miR-223 induces the expression of p21, p27 and the phospharylation of retinoblastoma, which are involved in the G1 block. We concluded that miR-223 functions as a tumor suppresser in osteosarcoma and miR-223/Ect2/p21 signaling is an important pathway that regulates the osteosarcoma cell cycle progression and proliferaion.
骨肉瘤是最常见的肿瘤之一。骨肉瘤的形成和发展机制已经研究了很长时间。最近，越来越多的证据表明 miRNA 在调节肿瘤生长中发挥着重要作用。在这项研究中，我们发现 miRNA-223 在骨肉瘤患者的肿瘤组织和骨肉瘤细胞系中均下调。miRNA-223 的过表达极大地抑制了 Saos-2 细胞的增殖。通过流式细胞术进行的细胞周期分析显示细胞周期停滞在 G1 期。进一步的机制研究表明，Ect2 是被 miR-223 直接靶向的。miR-223 下调 Ect2 诱导 p21、p27 的表达和视网膜母细胞瘤的磷酸化，这涉及到 G1 阻滞。我们得出结论，miR-223 在骨肉瘤中作为肿瘤抑制因子发挥作用，miR-223/Ect2/p21 信号通路是调节骨肉瘤细胞周期进展和增殖的重要途径。
