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综合转录组分析与实验验证确定lncRNA HOXA-AS2/miR-184/COL6A2为参与低级别胶质瘤复发的关键ceRNA调控机制。

Comprehensive Transcriptomic Analysis and Experimental Validation Identify lncRNA HOXA-AS2/miR-184/COL6A2 as the Critical ceRNA Regulation Involved in Low-Grade Glioma Recurrence.

作者信息

Chen Peng-Yu, Li Xiao-Dong, Ma Wei-Ning, Li Han, Li Miao-Miao, Yang Xin-Yu, Li Shao-Yi

机构信息

Department of Neurosurgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jun 3;13:4999-5016. doi: 10.2147/OTT.S245896. eCollection 2020.

DOI:10.2147/OTT.S245896
PMID:32581558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7276213/
Abstract

PURPOSE

The recurrence and metastasis of glioma are closely related to complex regulatory networks among protein-coding genes, lncRNAs and microRNAs. The aim of this study was to investigate core genes, lncRNAs, miRNAs and critical ceRNA regulatory mechanisms, which are involved in lower-grade glioma (LGG) recurrence.

MATERIALS AND METHODS

We employed multiple datasets from Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) to perform comprehensive transcriptomic analysis. Further in vitro experiments including cell proliferation assay, luciferase reporter assay, and Western blot were performed to validate our results.

RESULTS

Recurrent LGG and glioblastoma (GBM) showed different transcriptome characteristics with less overlap of differentially expressed protein-coding genes (DEPs), lncRNAs (DELs) and miRNAs (DEMs) compared with primary samples. There were no overlapping gene in ontology (GO) terms related to GBM recurrence in the TCGA and CGGA databases, but there were overlaps associated with LGG recurrence. GO analysis and protein-protein interaction (PPI) network analysis identified three core genes: TIMP1, COL1A1 and COL6A2. By hierarchical cluster analysis of them, LGGs could be clustered as Low_risk and High_risk group. The High_risk group with high expression of TIMP1, COL1A1, and COL6A2 showed worse prognosis. By coexpression networks analysis, competing endogenous RNA (ceRNA) network analysis, cell proliferation assay and luciferase reporter assay, we confirmed that lncRNA HOXA-AS2 functioned as a ceRNA for miR-184 to regulate expression of COL6A2, which induced cell proliferation of low-grade glioma.

CONCLUSION

In this study, we revealed a 3-hub protein-coding gene signature to improve prognostic prediction in LGG, and identified a critical ceRNA regulation involved in LGG recurrence.

摘要

目的

胶质瘤的复发和转移与蛋白质编码基因、长链非编码RNA（lncRNA）和微小RNA（miRNA）之间复杂的调控网络密切相关。本研究旨在探究参与低级别胶质瘤（LGG）复发的核心基因、lncRNA、miRNA及关键的竞争性内源RNA（ceRNA）调控机制。

材料与方法

我们使用了来自中国胶质瘤基因组图谱（CGGA）数据库和癌症基因组图谱（TCGA）的多个数据集进行全面的转录组分析。进一步进行了包括细胞增殖试验、荧光素酶报告基因试验和蛋白质免疫印迹法在内的体外实验以验证我们的结果。

结果

与原发性样本相比，复发性LGG和胶质母细胞瘤（GBM）表现出不同的转录组特征，差异表达的蛋白质编码基因（DEP）、lncRNA（DEL）和miRNA（DEM）的重叠较少。在TCGA和CGGA数据库中，与GBM复发相关的本体论（GO）术语中没有重叠基因，但存在与LGG复发相关的重叠。GO分析和蛋白质-蛋白质相互作用（PPI）网络分析确定了三个核心基因：金属蛋白酶组织抑制因子1（TIMP1）、Ⅰ型胶原α1链（COL1A1）和Ⅵ型胶原α2链（COL6A2）。通过对它们进行层次聚类分析，LGG可分为低风险组和高风险组。TIMP1、COL1A1和COL6A2高表达的高风险组预后较差。通过共表达网络分析、ceRNA网络分析、细胞增殖试验和荧光素酶报告基因试验，我们证实lncRNA HOXA-AS2作为miR-184的ceRNA发挥作用，调节COL6A2的表达，从而诱导低级别胶质瘤细胞增殖。

结论

在本研究中，我们揭示了一个三枢纽蛋白质编码基因特征以改善LGG的预后预测，并确定了一种参与LGG复发的关键ceRNA调控。

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2
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J Neurosurg. 2019 Jul 19;133(2):273-280. doi: 10.3171/2019.4.JNS183395. Print 2020 Aug 1.
3
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4
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FEBS Open Bio. 2023 Feb;13(2):307-322. doi: 10.1002/2211-5463.13541. Epub 2022 Dec 30.
5
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4
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5
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Biomed Pharmacother. 2019 Sep;117:109116. doi: 10.1016/j.biopha.2019.109116. Epub 2019 Jun 24.
6
Identification of prognostic markers for hepatocellular carcinoma based on miRNA expression profiles.基于 miRNA 表达谱鉴定肝癌的预后标志物。
Life Sci. 2019 Sep 1;232:116596. doi: 10.1016/j.lfs.2019.116596. Epub 2019 Jun 22.
7
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Aging (Albany NY). 2019 Jun 11;11(11):3811-3823. doi: 10.18632/aging.102018.
8
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9
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