Niu Guangfeng, Li Bin, Sun Li, An Chenggong
Department of Orthopaedics, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, P.R. China.
Department of Orthopaedics, Dingtao County Hospital, Dintao, P.R. China.
PLoS One. 2015 Mar 20;10(3):e0119225. doi: 10.1371/journal.pone.0119225. eCollection 2015.
Increasing evidence indicates that microRNAs (miRNAs), a class of small noncoding RNAs, participate in almost every step of cellular processes. MiRNAs are aberrantly expressed in human cancers and contribute to cancer development and progression. Study of miRNAs may provide a new clue for understanding the mechanism of carcinogenesis and a new tool for cancer treatment. In the present study, miR-153 was downregulated in human osteosarcoma tissues and cell lines. Introduction of miR-153 mimics into the MG-63 cells inhibited cell proliferation and invasion. Our results further revealed that transforming growth factor beta 2 (TGF-β2) was negatively regulated by miR-153. Furthermore, overexpression of miR-153 decreased p-SMAD2, p-SMAD3, epidermal growth factor receptor (EGFR) and insulin-like growth factor binding protein-3 (IGFBP-3) expressions, which were the downstream signaling molecules of TGF-β. Furthermore, miRNA-153 suppressed TGF-β-mediated MG-63 proliferation and migration. Therefore, our results suggest that miR-153 may act as a tumor suppressor in osteosarcoma through targeting TGF-β2.
越来越多的证据表明,微小RNA(miRNA)作为一类小的非编码RNA,几乎参与细胞过程的每一个步骤。miRNA在人类癌症中异常表达,并促进癌症的发生和发展。对miRNA的研究可能为理解致癌机制提供新线索,并为癌症治疗提供新工具。在本研究中,miR-153在人骨肉瘤组织和细胞系中表达下调。将miR-153模拟物导入MG-63细胞可抑制细胞增殖和侵袭。我们的结果进一步显示,转化生长因子β2(TGF-β2)受miR-153负调控。此外,miR-153的过表达降低了p-SMAD2、p-SMAD3、表皮生长因子受体(EGFR)和胰岛素样生长因子结合蛋白3(IGFBP-3)的表达,这些都是TGF-β的下游信号分子。此外,miRNA-153抑制TGF-β介导的MG-63增殖和迁移。因此,我们的结果表明,miR-153可能通过靶向TGF-β2在骨肉瘤中发挥肿瘤抑制作用。