Identification of Dysregulated microRNAs in Glioma Using RNA-sequencing
Identification of Dysregulated microRNAs in Glioma Using RNA-sequencing
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使用 RNA 测序鉴定神经胶质瘤中失调的 microRNA
DOI：
10.1007/s11596-021-2355-9
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发表时间：
2021-04-01
影响因子：
2.4
通讯作者：
Zhang, Qing-mei
中科院分区：
文献类型：
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作者：
Liu, Chang;Ge, Ying-ying;Zhang, Qing-mei
脑胶质瘤是中枢神经系统最常见的恶性肿瘤。尽管手术和放化疗等治疗方法取得了进展，但大多数患者容易复发，导致不良的临床结局。因此，有效的分子靶向治疗可能是胶质瘤治疗的一个有吸引力的策略。异常调节的microRNAs（miRNAs）被认为在胶质瘤的发生发展中起重要作用，是胶质瘤治疗的候选靶点之一。本研究旨在检测miRNAs在胶质瘤中的表达谱，为胶质瘤的治疗提供参考。首先，采用RNA测序技术（RNA-seq）检测5例正常脑组织、5例低度恶性胶质瘤（LGG）组织和5例胶质母细胞瘤（GBM）组织中miRNAs的表达谱。然后预测差异表达miRNAs（DEmiRNAs）的靶基因，并利用生物信息学技术进行GO富集和KEGG通路分析。最后，通过实时定量PCR（qRT-PCR）验证了在GBM和LGG中显著上调或下调的10个miRNAs。RNA-seq结果表明在胶质瘤中存在大量DEmiRNA。在LGG中有64个表达上调，17个表达下调;在GBM中有181个表达上调，124个表达下调。生物信息学分析表明，这些DEmiRNAs的靶基因在细胞代谢和发育等多种生物学过程和信号通路中富集。通过qRT-PCR进一步确认所选的DEmiRNA。miRNA-10 b-5 p、miRNA-92 b-3 p和miRNA-455- 5 p在GBM和LGG中均显著上调;而miRNA-542- 3 p在LGG中显著上调; miRNA-184和miRNA-206在GBM和LGG中均显著下调; miRNA-766- 5 p和miRNA-1- 3 p在GBM中显著下调。我们的研究表明，几种失调的miRNAs可能作为胶质瘤的潜在治疗靶点。
Glioma is the most common malignant brain tumor in central nervous system. Despite advances in the treatment of glioma such as surgery and chemoradiotherapy, most patients are easy to relapse, resulting in adverse clinical outcomes. Hence, effective molecular-targeting treatment may be one of attractive strategies for glioma therapy. The dysregulated microRNAs (miRNAs), one of the candidates of therapeutic targets, are believed to play an important role in the progression of glioma. In this study, we aimed to examine the expression profile of miRNAs in glioma and provide a reference for glioma therapy. Firstly, expression profile of miRNAs in 5 normal brain tissues, 5 low-grade glioma (LGG) tissues and 5 glioblastoma (GBM) tissues was detected by RNA sequencing (RNA-seq). Next, the target genes of differentially expressed miRNAs (DEmiRNAs) were predicted and then GO enrichment and KEGG pathway analysis performed by bioinformatics. Finally, 10 miRNAs which were significantly up- or down-regulated both in GBM and LGG were validated by real-time quantitative PCR (qRT-PCR). RNA-seq results indicated a number of DEmiRNAs in glioma. There were 64 up-regulated miRNAs and 17 down-regulated miRNAs in LGG, and 181 up-regulated miRNAs and 124 down-regulated miRNAs in GBM, respectively. Bioinformatics analysis showed that the target genes of these DEmiRNAs were enriched in various biological processes and signaling pathways such as cell metabolic and developmental process. Selected DEmiRNAs were further confirmed by qRT-PCR. miRNA-10b-5p, miRNA-92b-3p and miRNA-455-5p were significantly up-regulated in both GBM and LGG; while miRNA-542-3p was significantly up-regulated in LGG; miRNA-184 and miRNA-206 were significantly down-regulated in both GBM and LGG; miRNA-766-5p and miRNA-1-3p were significantly down-regulated in GBM. The subject of our study demonstrated several dysregulated miRNAs may serve as a potential therapeutic target for glioma.