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鉴定Glioma 中上皮-间充质转化相关的长非编码 RNA(LncRNA)特征。

Identification of an epithelial-mesenchymal transition related long non-coding RNA (LncRNA) signature in Glioma.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Scientific Research Center, East China Institute of Digital Medical Engineering, Shangrao, China.

出版信息

Bioengineered. 2021 Dec;12(1):4016-4031. doi: 10.1080/21655979.2021.1951927.

Abstract

Epithelial-mesenchymal transition (EMT)-related long non-coding RNAs (lncRNAs) may be exploited as potential therapeutic targets in gliomas. However, the prognostic value of EMT-related lncRNAs in gliomas is unclear. We obtained lncRNAs from The Cancer Genome Atlas and constructed EMT-related lncRNA co-expression networks to identify EMT-related lncRNAs. The Chinese Glioma Genome Atlas (CGGA) was used for validation. Gene set enrichment and principal component analyses were used for functional annotation. The EMT-lncRNA co-expression networks were constructed. A real-time quantitative polymerase chain reaction assay was performed to validate the bioinformatics results. A nine-EMT-related lncRNAs (HAR1A, LINC00641, LINC00900, MIR210HG, MIR22HG, PVT1, SLC25A21-AS1, SNAI3-AS1, and SNHG18) signature was identified in patients with glioma. Patients in the low-risk group had a longer overall survival (OS) than those in the high-risk group (P < 0.0001). Additionally, patients in the high-risk group showed no deletion of chromosomal arms 1p and/or 19q, isocitrate dehydrogenase wild type, and higher World Health Organization grade. Moreover, the signature was identified as an independent factor and was significantly associated with OS (P = 0.041, hazard ratio = 1.806). These findings were further validated using the CGGA dataset. The low- and high-risk groups showed different EMT statuses based on principal component analysis. To study the regulatory function of lncRNAs, a lncRNA-mediated ceRNA network was constructed, which showed that complex interactions of lncRNA-miRNA-mRNA may be a potential cause of EMT progression in gliomas. This study showed that the nine-EMT-related lncRNA signature has a prognostic value in gliomas.

摘要

上皮-间充质转化(EMT)相关的长链非编码 RNA(lncRNA)可能成为胶质瘤潜在的治疗靶点。然而,EMT 相关 lncRNA 在胶质瘤中的预后价值尚不清楚。我们从癌症基因组图谱(TCGA)中获取 lncRNA,并构建 EMT 相关 lncRNA 共表达网络来识别 EMT 相关 lncRNA。中国脑胶质瘤基因组图谱(CGGA)用于验证。基因集富集和主成分分析用于功能注释。构建 EMT-lncRNA 共表达网络。实时定量聚合酶链反应(qPCR)实验验证生物信息学结果。鉴定出胶质瘤患者存在 9 个 EMT 相关 lncRNAs(HAR1A、LINC00641、LINC00900、MIR210HG、MIR22HG、PVT1、SLC25A21-AS1、SNAI3-AS1 和 SNHG18)的特征。低危组患者的总生存期(OS)明显长于高危组(P<0.0001)。此外,高危组患者未发生 1p 和/或 19q 染色体臂缺失、异柠檬酸脱氢酶野生型和较高的世界卫生组织(WHO)分级。此外,该特征被确定为独立因素,与 OS 显著相关(P=0.041,风险比=1.806)。这些发现使用 CGGA 数据集进一步验证。基于主成分分析,低危组和高危组表现出不同的 EMT 状态。为了研究 lncRNA 的调控功能,构建了 lncRNA 介导的 ceRNA 网络,表明 lncRNA-miRNA-mRNA 的复杂相互作用可能是胶质瘤 EMT 进展的潜在原因。本研究表明,9 个 EMT 相关 lncRNA 特征在胶质瘤中具有预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/522b/8806607/fbf07229ff14/KBIE_A_1951927_UF0001_OC.jpg

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