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肺腺癌中 RBR E3 泛素连接酶的表达与预后的综合分析。

Comprehensive analysis of the expression and prognosis for RBR E3 ubiquitin ligases in lung adenocarcinoma.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Thorac Cancer. 2022 Sep;13(17):2459-2472. doi: 10.1111/1759-7714.14577. Epub 2022 Jul 12.

DOI:10.1111/1759-7714.14577
PMID:35820682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9436683/
Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and has a poor prognosis. RBR E3 ubiquitin ligases are a special class of E3 ubiquitin ligases which contain three zinc-bing domains that catalyze ubiquitin to substrate proteins. The RBR family of E3 ubiquitin ligases has been reported in various human malignancies, but the roles of RBR E3 ubiquitin ligases in LUAD remain unclear.

METHODS

By using TCGA and Kaplan-Meier plotter databases, we examined the expression and prognostic value of RBR E3 ubiquitin ligases. cBioPortal was used to analyze genetic mutations. The STRING database was used to build a protein interactive network. GO, KEGG, and GSEA were performed to investigate the potential biological functions of RBR E3 ubiquitin ligases.

RESULTS

The expression of ARIH2, RNF144B, RNF216, and RNF217 was significantly related to the clinicopathological parameters and prognosis in LUAD patients. GSEA enrichment result showed ARIH2, RNF144B, RNF216, and RNF217 were all associated with NADH dehydrogenase complex assembly. GO functional enrichment analysis revealed that four RBR E3 ubiquitin ligases and their interactors were most correlated with ubiquitin-protein transferase activity. KEGG pathway analysis indicated they were associated with cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway and NF-kappa B signaling pathway.

CONCLUSIONS

Our comprehensive bioinformatic analysis revealed that ARIH2, RNF144B, RNF216, and RNF217 may be new prognostic biomarkers and these findings will help to better understand the distinct roles of RBR E3 ubiquitin ligases in LUAD.

摘要

背景

肺腺癌（LUAD）是非小细胞肺癌中最常见的亚型，预后较差。RBR E3 泛素连接酶是一类特殊的 E3 泛素连接酶，包含三个锌结合域，可催化泛素与底物蛋白结合。RBR 家族的 E3 泛素连接酶已在多种人类恶性肿瘤中报道，但 RBR E3 泛素连接酶在 LUAD 中的作用尚不清楚。

方法

我们使用 TCGA 和 Kaplan-Meier plotter 数据库检查了 RBR E3 泛素连接酶的表达和预后价值。cBioPortal 用于分析遗传突变。STRING 数据库用于构建蛋白质相互作用网络。GO、KEGG 和 GSEA 用于研究 RBR E3 泛素连接酶的潜在生物学功能。

结果

ARIH2、RNF144B、RNF216 和 RNF217 的表达与 LUAD 患者的临床病理参数和预后显著相关。GSEA 富集结果表明，ARIH2、RNF144B、RNF216 和 RNF217 均与 NADH 脱氢酶复合物组装有关。GO 功能富集分析显示，四种 RBR E3 泛素连接酶及其相互作用物与泛素-蛋白转移酶活性最相关。KEGG 途径分析表明，它们与细胞质 DNA 感应途径、RIG-I 样受体信号通路和 NF-kappa B 信号通路有关。

结论

我们的综合生物信息学分析表明，ARIH2、RNF144B、RNF216 和 RNF217 可能是新的预后生物标志物，这些发现将有助于更好地理解 RBR E3 泛素连接酶在 LUAD 中的独特作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/22fea240f333/TCA-13-2459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/f35b7a4c04ed/TCA-13-2459-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/35be743dfd9c/TCA-13-2459-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/84ed2ca51a14/TCA-13-2459-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/3b01ef07d8a1/TCA-13-2459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/5398044783c3/TCA-13-2459-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/e0b859a581ca/TCA-13-2459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/bf2aa53735f5/TCA-13-2459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/22fea240f333/TCA-13-2459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/f35b7a4c04ed/TCA-13-2459-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/35be743dfd9c/TCA-13-2459-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/84ed2ca51a14/TCA-13-2459-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/3b01ef07d8a1/TCA-13-2459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/5398044783c3/TCA-13-2459-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/e0b859a581ca/TCA-13-2459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/bf2aa53735f5/TCA-13-2459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/365e/9436683/22fea240f333/TCA-13-2459-g004.jpg

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