Upregulation of long noncoding RNA HOXA-AS3 promotes tumor progression and predicts poor prognosis in glioma.
Upregulation of long noncoding RNA HOXA-AS3 promotes tumor progression and predicts poor prognosis in glioma.
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长链非编码RNA HOXA-AS3的上调促进肿瘤进展并预测神经胶质瘤的不良预后
DOI：
10.18632/oncotarget.18162
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发表时间：
2017-08-08
期刊：
影响因子：
--
通讯作者：
Jiang T
中科院分区：
文献类型：
--
作者：
Wu F;Zhang C;Cai J;Yang F;Liang T;Yan X;Wang H;Wang W;Chen J;Jiang T
最近，长非编码RNA(LncRNAs)已成为许多癌症的新的潜在治疗靶点。然而，它们的预后价值和与胶质瘤相关的生物学功能仍有待阐明。在这里，高通量RNAseq被用来检测325个人脑胶质瘤组织中lncRNAs的表达谱。研究表明，一个新的LncRNA Hoxa-AS3是胶质瘤组织中表达最显著的LncRNAs之一。定量聚合酶链式反应进一步证实了HOXA-AS3在患者样本和胶质瘤细胞系中的表达增加。单因素和多因素Cox回归分析显示，HOXA-AS3是影响脑胶质瘤患者预后的独立因素。基因集浓缩分析表明，与HOXA-AS3表达相关的基因集参与了细胞周期进程和E2F靶点的形成。在功能上，Hoxa-AS3沉默通过改变细胞周期进程和促进细胞凋亡而导致细胞增殖停滞，并损害胶质瘤细胞的迁移。此外，Hoxa-AS3基因敲除对异种移植小鼠的生长也有抑制作用。我们的结果强调了Hoxa-AS3在胶质瘤进展中的重要作用，并表明Hoxa-AS3可能是一种有价值的胶质瘤预后生物标志物。
Long noncoding RNAs (lncRNAs) have recently emerged as new potentially promising therapeutic targets in many cancers. However, their prognostic value and biological functions associated with glioma remain to be elucidated. Here, High-throughput RNAseq was performed to detect the expression profiles of lncRNAs in 325 human glioma tissues. It was shown that a novel lncRNA HOXA-AS3 was one of the most significantly upregulated lncRNAs in glioma tissues. Quantitative PCR further verified the increased expression of HOXA-AS3 in patient samples and glioma cell lines. Uni and Multivariate Cox regression analysis revealed that HOXA-AS3 was an independent prognostic factor in glioma patients. Gene set enrichment analysis indicated that the gene sets correlated with HOXA-AS3 expression were involved in cell cycle progression and E2F targets. Functionally, HOXA-AS3 silencing resulted in proliferation arrest by altering cell cycle progression and promoting cell apoptosis, and impaired cell migration in glioma cells. Furthermore, the growth-inhibiting effect of HOXA-AS3 knockdown was also demonstrated in Xenograft mouse model. Our results highlight the important role of HOXA-AS3 in glioma progression, and indicate that HOXA-AS3 may be served as a valuable prognostic biomarker for glioma.
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