A novel cell cycle-associated IncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma
A novel cell cycle-associated IncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma
复制标题
一种新型的细胞周期相关 lncRNA HOXA11-AS，从 HOXA 转录物的 5 引物末端转录而来，是神经胶质瘤进展的生物标志物
DOI：
10.1016/j.canlet.2016.01.039
复制
发表时间：
2016-04-10
期刊：
影响因子：
9.7
通讯作者：
Han, Lei
中科院分区：
文献类型：
--
作者：
Wang, Qixue;Zhang, Junxia;Han, Lei
神经胶质瘤中全面的 incRNA 表达特征尚未完全阐明。我们进行了高通量微阵列检测 220 个人类神经胶质瘤组织的 ncRNA 表达谱。在这里，我们发现一种新的 IncRNA HOXA11-AS 是 HOX11 基因的反义转录本。结果表明HOXA11-AS与胶质瘤分级和不良预后密切相关。多因素Cox回归分析显示HOXA11-AS是多形性胶质母细胞瘤患者的独立预后因素，其表达与癌症基因组图谱的胶质瘤分子亚型相关。基因集富集分析表明与 HOXA11-AS 表达最相关的基因集参与细胞周期进展。 HOXA11-AS 转录物的过度表达在体外促进细胞增殖，而 HOXA11-AS 表达的敲低则通过调节细胞周期进程来抑制细胞增殖。 HOXA11-AS 的生长促进和生长抑制作用也在异种移植小鼠模型中得到证实。我们的数据首次证实 HOXA11-AS 是一种重要的长非编码 RNA，主要作为神经胶质瘤患者生存的预后因素。 HOXA11-AS可以作为识别神经胶质瘤分子亚型的生物标志物和神经胶质瘤患者的治疗靶点。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
The comprehensive incRNA expression signature in glioma has not yet been fully elucidated. We performed a high-throughput microarray to detect the ncRNA expression profiles of 220 human glioma tissues. Here, we found that a novel IncRNA, HOXA11-AS, was the antisense transcript of the HOX11 gene. It was shown that HOXA11-AS was closely associated with glioma grade and poor prognosis. Multivariate Cox regression analysis revealed that HOXA11-AS was an independent prognostic factor in glioblastoma multiforme patients, and its expression was correlated with the glioma molecular subtypes of the Cancer Genome Atlas. Gene set enrichment analysis indicated that the gene sets most correlated with HOXA11-AS expression were involved in cell cycle progression. Over-expression of the HOXA11-AS transcript promoted cell proliferation in vitro, while knockdown of HOXA11-AS expression repressed cell proliferation via regulation of cell cycle progression. The growth-promoting and growth-inhibiting effects of HOXA11-AS were also demonstrated in a xenograft mouse model. Our data confirms, for the first time, that HOXA11-AS is an important long non-coding RNA that primarily serves as a prognostic factor for glioma patient survival. HOXA11-AS could serve as a biomarker for identifying glioma molecular subtypes and as therapeutic target for glioma patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.