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构建和分析 lncRNA-miRNA-mRNA ceRNA 网络鉴定出一个包含八个基因的特征作为肾乳头细胞癌(KIRP)潜在的预后因素。

Construction and Analysis of lncRNA-miRNA-mRNA ceRNA Network Identify an Eight-Gene Signature as a Potential Prognostic Factor in Kidney Renal Papillary Cell Carcinoma (KIRP).

出版信息

Altern Ther Health Med. 2022 Sep;28(6):42-51.

Abstract

AIMS

This study was conducted to establish the potential competing endogeneous RNA (ceRNA) network for predicting prognoses in kidney papillary renal cell carcinoma (KIRP) and explore novel therapeutic targets.

METHODS

The edgeR package in R was used to determine differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), based on data from The Cancer Gene Atlas Program (TCGA) and the Genotype Expression (GTEx) databases. Weighted gene co-expression network analysis (WGCNA) was performed to filter out the mRNAs or lncRNAs that were strongly related to KIRP. The miRNAs that possibly sponged by differentially expressed RNAs lncRNAs (DElncRNAs) were screened using miRcode. Starbase, miRDB, and TargetScan sets were utilized to predict target mRNAs to corresponding miRNAs. LASSO and multivariate Cox regression analyses were applied for the determination of potential prognostic significance. Finally, the lncRNA-miRNA-mRNA ceRNA network was constructed.

RESULTS

A total of 1739 DEmRNAs and 1599 DElncRNAs were identified in KIRP. WGCNA analysis suggested that DEmRNAs in the blue module and DElncRNAs in the turquoise module were closely correlated with KIRP. An 8-gene signature was constructed, which had prognostic significance and predictive value in KIRP. Of note, a lncRNA-miRNA-mRNA ceRNA network (including 18 lncRNAs, 5 miRNAs, and 7 mRNAs) was established.

CONCLUSION

This investigation constructed a new lncRNA-miRNA-mRNA ceRNA network, and proposed some genes that may be novel targets, as well as a theoretical basis for the treatment of patients with KIRP.

摘要

目的

本研究旨在建立潜在的竞争内源性 RNA(ceRNA)网络,以预测肾乳头肾细胞癌(KIRP)的预后,并探索新的治疗靶点。

方法

基于癌症基因图谱计划(TCGA)和基因型表达(GTEx)数据库的数据,使用 R 中的 edgeR 软件包确定差异表达的信使 RNA(mRNA)、长非编码 RNA(lncRNA)和 microRNA(miRNA)。采用加权基因共表达网络分析(WGCNA)筛选与 KIRP 强相关的 mRNA 或 lncRNA。利用 miRcode 筛选可能由差异表达 RNA lncRNA(DElncRNA)sponged 的 miRNA。使用 Starbase、miRDB 和 TargetScan 集预测相应 miRNA 的靶 mRNA。应用 LASSO 和多变量 Cox 回归分析确定潜在的预后意义。最后,构建 lncRNA-miRNA-mRNA ceRNA 网络。

结果

在 KIRP 中共鉴定出 1739 个 DEmRNA 和 1599 个 DElncRNA。WGCNA 分析表明,蓝色模块中的 DEmRNA 和绿松石模块中的 DElncRNA 与 KIRP 密切相关。构建了一个具有预后意义和预测价值的 8 基因特征。值得注意的是,构建了一个 lncRNA-miRNA-mRNA ceRNA 网络(包括 18 个 lncRNA、5 个 miRNA 和 7 个 mRNA)。

结论

本研究构建了一个新的 lncRNA-miRNA-mRNA ceRNA 网络,提出了一些可能是新的治疗靶点的基因,为 KIRP 患者的治疗提供了理论依据。

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