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长链非编码RNA XIST通过充当miR-429的分子海绵促进胶质瘤的致瘤性和血管生成。

Long Non-coding RNA XIST Promotes Glioma Tumorigenicity and Angiogenesis by Acting as a Molecular Sponge of miR-429.

作者信息

Cheng Zhihua, Li Zhenshengnan, Ma Ke, Li Xiaoyu, Tian Nan, Duan Jinyue, Xiao Xu, Wang Yi

机构信息

Department of Vascular Surgery, the First Hospital of Jilin University, Changchun, 130021, P.R. China.

Department of Clinical Medicine, Norman Bethune Health Science Center of Jilin University, Changchun, 130021,P.R. China.

出版信息

J Cancer. 2017 Nov 6;8(19):4106-4116. doi: 10.7150/jca.21024. eCollection 2017.

Abstract

Glioma is a worldwide malignancy, which displays significantly active metastasis and angiogenesis. Interaction between long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) has been shown to play crucial role in regulating tumor properties. However, the potential of lncRNA X-inactive specific transcript (XIST) to function as a miRNA regulator and its relevance in glioma tumorigenicity and angiogenesis have so far remained unclear. Expression analysis of lncRNA XIST in glioma cells revealed its significant up-regulation. Interestingly, silencing of XIST repressed both metastatic and pro-angiogenic ability as well as . Subsequent studies revealed that lncRNA XIST expression inversely correlated with miR-429 expression in glioma cells; miR-429 modulated XIST expression by directly targeting the XIST gene sequence. In addition, miR-429 inhibitor restored metastatic and pro-angiogenic ability of gliomas abolished by silencing XIST. Our data provide insight into the key roles of the lncRNA-miRNA functional network in gliomas, which can aid in developing new therapeutic strategies for gliomas through clinical trials.

摘要

神经胶质瘤是一种全球性的恶性肿瘤,具有显著活跃的转移和血管生成能力。长链非编码RNA(lncRNA)与微小RNA(miRNA)之间的相互作用已被证明在调节肿瘤特性中起关键作用。然而,lncRNA X失活特异性转录本(XIST)作为miRNA调节因子的潜力及其在神经胶质瘤致瘤性和血管生成中的相关性迄今仍不清楚。对神经胶质瘤细胞中lncRNA XIST的表达分析显示其显著上调。有趣的是,XIST沉默抑制了转移能力和促血管生成能力以及……。随后的研究表明,lncRNA XIST的表达与神经胶质瘤细胞中miR-429的表达呈负相关;miR-429通过直接靶向XIST基因序列来调节XIST的表达。此外,miR-429抑制剂恢复了因XIST沉默而被消除的神经胶质瘤的转移和促血管生成能力。我们的数据揭示了lncRNA-miRNA功能网络在神经胶质瘤中的关键作用,这有助于通过临床试验开发针对神经胶质瘤的新治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208d/5706014/f0b839d857de/jcav08p4106g001.jpg

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