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基于加权基因共表达网络分析构建用于葡萄膜黑色素瘤预后的新型 lncRNA-miRNA-mRNA 竞争内源性 RNA 网络。

A novel lncRNA-miRNA-mRNA competitive endogenous RNA network for uveal melanoma prognosis constructed by weighted gene co-expression network analysis.

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China.

出版信息

Life Sci. 2020 Nov 1;260:118409. doi: 10.1016/j.lfs.2020.118409. Epub 2020 Sep 11.

Abstract

AIMS

Uveal melanoma (UM) is the most common and aggressive intraocular tumor in adults, and long-term survival of UM patients remains poor. Abnormal competitive endogenous RNA (ceRNA) networks promote the initiation and progression of many tumors and may thus serve as useful prognostic indicators. Here, we do a comprehensive analysis of long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA ceRNA networks as prognostic markers for UM.

MATERIALS AND METHODS

The Cancer Genome Atlas UM dataset was used to identify survival-related mRNA and lncRNA modules through weighted gene co-expression network analysis (WGCNA). Prognostic miRNAs were identified using univariate Cox proportional hazard regression. We then used Cox and least absolute shrinkage and selection operator regression to screen for prognostic hub mRNAs and establish a hub ceRNA network. A nomogram of five hub mRNAs was constructed and Kaplan-Meier survival analysis performed.

KEY FINDINGS

Six mRNA modules were constructed, two of which involved 1490 mRNAs that significantly correlated with survival. Among the three lncRNA modules constructed, one involved 199 survival-related lncRNAs. Five hub prognostic mRNAs were identified and a hub ceRNA network constructed, consisting of six lncRNAs, four miRNAs, and five mRNAs, with high prognostic value.

SIGNIFICANCE

We describe a hub ceRNA network of survival-associated lncRNAs, miRNAs, and mRNA that may underlie a critical post-translational regulatory mechanism determining UM aggression. These hub RNAs may be valuable prognostic markers and therapeutic targets in UM.

摘要

目的

葡萄膜黑色素瘤(UM)是成年人中最常见且侵袭性最强的眼内肿瘤,UM 患者的长期生存率仍然较差。异常的竞争性内源性 RNA(ceRNA)网络促进了许多肿瘤的发生和进展,因此可能成为有用的预后指标。在这里,我们全面分析了长非编码 RNA(lncRNA)-微小 RNA(miRNA)-mRNA ceRNA 网络作为 UM 的预后标志物。

材料和方法

使用癌症基因组图谱 UM 数据集通过加权基因共表达网络分析(WGCNA)鉴定与生存相关的 mRNA 和 lncRNA 模块。使用单变量 Cox 比例风险回归鉴定预后 miRNA。然后,我们使用 Cox 和最小绝对收缩和选择算子回归筛选预后关键 mRNAs 并建立关键 ceRNA 网络。构建了五个关键 mRNAs 的列线图并进行 Kaplan-Meier 生存分析。

主要发现

构建了六个 mRNA 模块,其中两个包含 1490 个与生存显著相关的 mRNAs。在构建的三个 lncRNA 模块中,有一个涉及 199 个与生存相关的 lncRNA。鉴定出五个关键预后 mRNAs,并构建了一个关键 ceRNA 网络,该网络由六个 lncRNA、四个 miRNA 和五个 mRNA 组成,具有较高的预后价值。

意义

我们描述了一个与生存相关的 lncRNA、miRNA 和 mRNA 的关键 ceRNA 网络,该网络可能构成了决定 UM 侵袭性的关键翻译后调控机制。这些关键 RNA 可能是 UM 有价值的预后标志物和治疗靶点。

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