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一项全面的多组学分析通过Notch信号通路中的RNA相互作用揭示了与癌症相关的分子特征。

A comprehensive multi-omics analysis reveals molecular features associated with cancer via RNA cross-talks in the Notch signaling pathway.

作者信息

Guo Li, Li Sunjing, Yan Xiaoqiang, Shen Lulu, Xia Daoliang, Xiong Yiqi, Dou Yuyang, Mi Lan, Ren Yujie, Xiang Yangyang, Ren Dekang, Wang Jun, Liang Tingming

机构信息

Department of Bioinformatics, Smart Health Big Data Analysis and Location Services Engineering Lab of Jiangsu Province, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China.

出版信息

Comput Struct Biotechnol J. 2022 Jul 26;20:3972-3985. doi: 10.1016/j.csbj.2022.07.036. eCollection 2022.

Abstract

The Notch signaling has an important role in multiple cellular processes and is related to carcinogenic process. To understand the potential molecular features of the crucial Notch pathway, a comprehensive multi-omics analysis is performed to explore its contributions in cancer, mainly including analysis of somatic mutation landscape, pan-cancer expression, ncRNA regulation and potential prognostic power. The screened 22 Notch core genes are relative stable in DNA variation. Dynamic expression patterns are associated with the Notch activity, which are mainly regulated by multiple ncRNAs via interactions of ncRNA:mRNA and ceRNA networks. The Notch pathway shows a potential prognostic ability through integrating multi-omics features as well as their targets, and it is correlated with immune infiltration and maybe available drug targets, implying the potential role in individualized treatment. Collectively, all of these findings contribute to exploring crucial role of the key pathway in cancer pathophysiology and gaining mechanistic insights into cross-talks among RNAs and biological pathways, which indicates the possible application of the well-conserved Notch signaling pathway in precision medicine.

摘要

Notch信号在多种细胞过程中发挥重要作用,且与致癌过程相关。为了解关键Notch通路的潜在分子特征,进行了全面的多组学分析以探究其在癌症中的作用,主要包括体细胞突变图谱分析、泛癌表达分析、非编码RNA调控分析以及潜在的预后能力分析。筛选出的22个Notch核心基因在DNA变异方面相对稳定。动态表达模式与Notch活性相关,其主要由多种非编码RNA通过非编码RNA:mRNA和竞争性内源RNA网络的相互作用进行调控。Notch通路通过整合多组学特征及其靶点显示出潜在的预后能力,并且与免疫浸润相关,可能还是有效的药物靶点,这暗示了其在个体化治疗中的潜在作用。总体而言,所有这些发现有助于探索关键通路在癌症病理生理学中的关键作用,并深入了解RNA与生物通路之间的相互作用机制,这表明保守的Notch信号通路在精准医学中可能具有应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0760/9340535/f87c4543644b/ga1.jpg

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