Department of Neurology, The 148 Central Hospital of PLA, Zibo City, Shandong Province, China.
Department of Neurology, The 148 Central Hospital of PLA, Zibo City, Shandong Province, China.
Cancer Lett. 2015 Oct 28;367(2):122-8. doi: 10.1016/j.canlet.2015.03.027. Epub 2015 Mar 23.
The transcripts of the gene Colorectal Neoplasia Differentially Expressed (CRNDE) are recognized as long-noncoding RNAs (lncRNAs), which are expressed in specific regions within the human brain, and are the most upregulated lncRNA in gliomas. However, the underlying regulation and function of CRNDE in gliomas are largely unknown. In this study, the upregulation of CRNDE was confirmed in both primary specimens from glioma patients and in vitro with cell lines. Overexpression of specific CRNDE transcript promotes cell growth and migration in vitro while knockdown of CRNDE expression manifests a repressive function during these cellular processes. The growth promoting effect of CRNDE was also demonstrated in a xenograft mouse model. Mechanistic studies further revealed that histone acetylation in the promoter region might account for the upregulation of CRNDE, and the level of CRNDE expression could be modulated by mammalian Target of Rapamycin (mTOR) signaling in glioma. Thus, our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of glioma.
CRNDE 基因的转录本被认为是长链非编码 RNA（lncRNA），它们在人类大脑的特定区域表达，是神经胶质瘤中上调最明显的 lncRNA。然而，CRNDE 在神经胶质瘤中的潜在调控和功能在很大程度上是未知的。在这项研究中，CRNDE 的上调在来自神经胶质瘤患者的原发性标本和体外细胞系中均得到了证实。特定 CRNDE 转录本的过表达促进了体外细胞的生长和迁移，而 CRNDE 表达的敲低在这些细胞过程中表现出抑制作用。CRNDE 的促生长作用在异种移植小鼠模型中也得到了证明。机制研究进一步表明，启动子区域的组蛋白乙酰化可能是 CRNDE 上调的原因，并且在神经胶质瘤中，CRNDE 的表达水平可以被哺乳动物雷帕霉素靶蛋白（mTOR）信号调节。因此，我们的研究结果表明，CRNDE 可作为治疗神经胶质瘤的潜在新型治疗靶点。
