He Wenbo, Feng Lin, Xia Dongliang, Han Nuan
Department of Pediatric Surgery, Affiliated Hospital of Jining Medical University Jining 272029, Shandong Province, People's Republic of China.
Department of Pediatric Surgery, Central Hospital of Tai'an Tai'an 271000, Shandong Province, People's Republic of China.
Int J Clin Exp Med. 2015 Mar 15;8(3):3482-9. eCollection 2015.
MiRNAs play crucial roles in development of cancer. However, the underlying mechanisms of miRNAs in osteosarcoma (OS) are poorly understood. In the present study, we reported that the expression of miR-374a was markedly upregulated in OS tissues and OS cells compared with the matched adjacent normal tissues and human osteoclast h-FOB cell lines. Overexpression of miR-374a promoted the proliferation and anchorage-independent growth of OS cells, whereas inhibition of miR-374a showed opposite effect. Furthermore, we identified that FOXO1 is the functional target of miR-374a. MiR-374a-induced proliferation was correlated with FOXO1, upregulating of the cell cycle regulator cyclin D1 and downregulating of cyclin-dependent kinase inhibitors p27. In functional assays, FOXO1 downregulation is required for miR-374a-induced OS cell proliferation. In sum, our data provide compelling evidence that a novel mechanism of FOXO1 suppression mediated by miR-374a in OS.
微小RNA（miRNAs）在癌症发展过程中发挥着关键作用。然而，miRNAs在骨肉瘤（OS）中的潜在机制仍知之甚少。在本研究中，我们报告称，与配对的相邻正常组织和人破骨细胞h-FOB细胞系相比，miR-374a在OS组织和OS细胞中的表达明显上调。miR-374a的过表达促进了OS细胞的增殖和非锚定依赖性生长，而抑制miR-374a则产生相反的效果。此外，我们确定FOXO1是miR-374a的功能靶点。miR-374a诱导的增殖与FOXO1相关，上调细胞周期调节因子细胞周期蛋白D1并下调细胞周期蛋白依赖性激酶抑制剂p27。在功能试验中，miR-374a诱导的OS细胞增殖需要下调FOXO1。总之，我们的数据提供了令人信服的证据，证明miR-374a在OS中介导的FOXO1抑制的新机制。
