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一种新型的细胞周期相关长链非编码RNA,HOXA11-AS,从HOXA转录本的5'端转录而来,是胶质瘤进展的生物标志物。

A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma.

作者信息

Wang Qixue, Zhang Junxia, Liu Yanwei, Zhang Wei, Zhou Junhu, Duan Ran, Pu Peiyu, Kang Chunsheng, Han Lei

机构信息

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China.

Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

出版信息

Cancer Lett. 2016 Apr 10;373(2):251-9. doi: 10.1016/j.canlet.2016.01.039. Epub 2016 Jan 29.

Abstract

The comprehensive lncRNA 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 lncRNA, 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.

摘要

胶质瘤中lncRNA的综合表达特征尚未完全阐明。我们进行了一项高通量微阵列检测220例人类胶质瘤组织的ncRNA表达谱。在此,我们发现一种新的lncRNA,HOXA11-AS,是HOX11基因的反义转录本。研究表明,HOXA11-AS与胶质瘤分级及预后不良密切相关。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中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程。HOXA11-AS转录本的过表达促进体外细胞增殖,而敲低HOXA11-AS表达则通过调节细胞周期进程抑制细胞增殖。HOXA11-AS的促生长和抑生长作用在异种移植小鼠模型中也得到证实。我们的数据首次证实,HOXA11-AS是一种重要的长链非编码RNA,主要作为胶质瘤患者生存的预后因素。HOXA11-AS可作为识别胶质瘤分子亚型的生物标志物及胶质瘤患者的治疗靶点。

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