Identification of Grade-associated MicroRNAs in Brainstem Gliomas Based on Microarray Data
Identification of Grade-associated MicroRNAs in Brainstem Gliomas Based on Microarray Data
复制标题
基于微阵列数据鉴定脑干胶质瘤中与级别相关的 MicroRNA。
DOI：
10.7150/jca.26417
复制
发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Zhang, Liwei
中科院分区：
文献类型：
--
作者：
Chen, Xin;Dong, Dezuo;Zhang, Liwei
脑干胶质瘤是一种罕见的肿瘤，难以手术切除，与脑干胶质瘤（BSG）相关的microRNA（miRNA）和信号通路在很大程度上是未知的。为了鉴定BSG中的分级相关miRNA，在本研究中对10个低分级和15个高分级BSG进行了微阵列分析。鉴定差异表达的miRNA（DE-miRNA），并选择功能性DE-miRNA。分析了潜在的靶基因和富集途径，并生成了靶基因相关蛋白质-蛋白质相互作用（PPI）网络。通过实时定量PCR确认等级相关的功能性DE-miRNAs。首先，鉴定了28种功能性DE-miRNAs，包括13种上调的miRNAs和15种下调的miRNAs。第二，筛选了2546个参与BSG相关通路的靶基因，如调节干细胞多能性的信号通路、AMPK信号通路、HIF-1信号通路、PI 3 K-Akt信号通路、Wnt信号通路和Hippo信号通路。第三，PHLPP 2和VEGFA被鉴定为PPI网络中的枢纽基因。最后，我们发现hsa-miR-34 a-5 p抑制BSG细胞的体外侵袭。综上所述，本研究通过生物信息学的综合分析，确定了BSGs分级相关功能性DE-miRNAs的潜在靶基因和作用途径，有助于提高BSGs预后评估的准确性。此外，这些枢纽基因和途径可能是治疗BSG的治疗靶点。
Gliomas arising in the brainstem are rare tumours that are difficult to surgically resect, and the microRNAs (miRNAs) and signalling pathways associated with brainstem gliomas (BSGs) are largely unknown. To identify grade-associated miRNAs in BSGs, a microarray analysis of 10 low-grade and 15 high-grade BSGs was performed in this study. Differentially expressed miRNAs (DE-miRNAs) were identified, and the functional DE-miRNAs were selected. The potential target genes and enriched pathways were analysed, and a target gene-associated protein-protein interaction (PPI) network was generated. Grade-associated functional DE-miRNAs were confirmed by real-time quantitative PCR. First, 28 functional DE-miRNAs, including 13 upregulated miRNAs and 15 downregulated miRNAs, were identified. Second, 2546 target genes that were involved in BSG-related pathways, such as signalling pathways regulating the pluripotency of stem cells, the AMPK signalling pathway, the HIF-1 signalling pathway, the PI3K-Akt signalling pathway, the Wnt signalling pathway and the Hippo signalling pathway, were screened. Third, PHLPP2 and VEGFA were identified as hub genes in the PPI network. Last, we found that hsa-miR-34a-5p inhibits BSG cell invasion in vitro. In summary, using integrated bioinformatics analysis, we have identified the potential target genes and pathways of grade-associated functional DE-miRNAs in BSGs, which could improve the accuracy of prognostic evaluation. Furthermore, these hub genes and pathways could be therapeutic targets for the treatment of BSGs.