Department of Emergency, the First Affiliated Hospital of Xi'an Medical University, Xi'an City, Shaanxi, China.
Department of Cardiovascular Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, Shaanxi, China.
Exp Mol Pathol. 2018 Feb;104(1):19-25. doi: 10.1016/j.yexmp.2017.12.002. Epub 2017 Dec 12.
Osteosarcoma is the most common bone malignancy in adolescence. Recently, the long non-coding RNAs (lncRNAs) were reported to play important roles in osteosarcoma progression. The present study examined the potential role of the lncRNA, Colorectal Neoplasia Differentially Expressed (CRNDE) and molecular mechanisms underlying osteosarcoma progression. In the present study, we identified that CRNDE was up-regulated in osteosarcoma tissues and cell lines, and CRNDE expression level was significantly higher in osteosarcoma tissues from patients with advanced stage and metastasis. Overexpression of CRNDE promoted cell growth, cell proliferation, cell invasion and migration, and increased cell population at S phase with a decreased cell population at G/G phase in MG-63 cells. Knock-down of CRNDE suppressed cell growth, cell proliferation, cell invasion and migration, and decreased cell population at S phase with an increased cell population at G/G phase in U2OS cells. Overexpression of CRNDE was found to enhance the activity of Notch1 signaling and promote epithelial-mesenchymal transition (EMT) in MG-63 cells, while knock-down of CRNDE exerted the opposite effects in U2OS cells. The in vivo results showed that knock-down of CRNDE suppressed the tumor growth in the nude mice inoculated with osteosarcoma cells, and knock-down of CRNDE also suppressed the mRNA expression of Notch1, JAG1, N-cadherin, vimentin, and increased the mRNA expression of E-cadherin in the tumor tissues. Collectively, our results indicated that CRNDE functioned as an oncogene in osteosarcoma cell lines, and CRNDE may exert its oncogenic role via regulating Notch1 signaling and EMT in osteosarcoma.
骨肉瘤是青少年中最常见的骨恶性肿瘤。最近，长链非编码 RNA（lncRNA）被报道在骨肉瘤进展中发挥重要作用。本研究探讨了 lncRNA 结直肠肿瘤差异表达（CRNDE）在骨肉瘤进展中的潜在作用及其分子机制。在本研究中，我们鉴定出 CRNDE 在骨肉瘤组织和细胞系中上调，并且 CRNDE 的表达水平在晚期和转移的骨肉瘤患者组织中显著更高。CRNDE 的过表达促进了 MG-63 细胞的细胞生长、细胞增殖、细胞侵袭和迁移，并增加了 S 期细胞群体，降低了 G1/G0 期细胞群体。U2OS 细胞中 CRNDE 的敲低抑制了细胞生长、细胞增殖、细胞侵袭和迁移，并增加了 G1/G0 期细胞群体，降低了 S 期细胞群体。过表达 CRNDE 被发现增强了 Notch1 信号的活性，并促进了 MG-63 细胞中的上皮-间充质转化（EMT），而 CRNDE 的敲低在 U2OS 细胞中则产生了相反的效果。体内结果表明，CRNDE 的敲低抑制了裸鼠接种骨肉瘤细胞后的肿瘤生长，并且 CRNDE 的敲低还抑制了肿瘤组织中 Notch1、JAG1、N-钙粘蛋白、波形蛋白的 mRNA 表达，增加了 E-钙粘蛋白的 mRNA 表达。综上所述，我们的结果表明，CRNDE 在骨肉瘤细胞系中作为癌基因发挥作用，并且 CRNDE 可能通过调节 Notch1 信号和 EMT 在骨肉瘤中发挥其致癌作用。
