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优化与癌症转移相关的预后关键微小RNA-靶标相互作用。

Optimizing prognosis-related key miRNA-target interactions responsible for cancer metastasis.

作者信息

Zhao Hongying, Yuan Huating, Hu Jing, Xu Chaohan, Liao Gaoming, Yin Wenkang, Xu Liwen, Wang Li, Zhang Xinxin, Shi Aiai, Li Jing, Xiao Yun

机构信息

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

Department of Ultrasonic Medicine, The 1st Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China.

出版信息

Oncotarget. 2017 Nov 27;8(65):109522-109535. doi: 10.18632/oncotarget.22724. eCollection 2017 Dec 12.

DOI:10.18632/oncotarget.22724
PMID:29312626
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5752539/
Abstract

Increasing evidence suggests that the abnormality of microRNAs (miRNAs) and their downstream targets is frequently implicated in the pathogenesis of human cancers, however, the clinical benefit of causal miRNA-target interactions has been seldom studied. Here, we proposed a computational method to optimize prognosis-related key miRNA-target interactions by combining transcriptome and clinical data from thousands of TCGA tumors across 16 cancer types. We obtained a total of 1,956 prognosis-related key miRNA-target interactions between 112 miRNAs and 1,443 their targets. Interestingly, these key target genes are specifically involved in tumor progression-related functions, such as 'cell adhesion' and 'cell migration'. Furthermore, they are most significantly correlated with 'tissue invasion and metastasis', a hallmark of metastasis, in ten distinct types of cancer through the hallmark analysis. These results implicated that the prognosis-related key miRNA-target interactions were highly associated with cancer metastasis. Finally, we observed that the combination of these key miRNA-target interactions allowed to distinguish patients with good prognosis from those with poor prognosis both in most TCGA cancer types and independent validation sets, highlighting their roles in cancer metastasis. We provided a user-friendly database named miRNATarget (freely available at http://biocc.hrbmu.edu.cn/miRNATar/), which provides an overview of the prognosis-related key miRNA-target interactions across 16 cancer types.

摘要

越来越多的证据表明，微小RNA（miRNA）及其下游靶点的异常经常与人类癌症的发病机制有关，然而，因果性miRNA-靶点相互作用的临床益处很少被研究。在此，我们提出了一种计算方法，通过整合来自16种癌症类型的数千个TCGA肿瘤的转录组和临床数据，来优化与预后相关的关键miRNA-靶点相互作用。我们总共获得了112个miRNA与其1443个靶点之间的1956个与预后相关的关键miRNA-靶点相互作用。有趣的是，这些关键靶基因特别参与肿瘤进展相关的功能，如“细胞黏附”和“细胞迁移”。此外，通过特征分析，它们在十种不同类型的癌症中与转移的一个标志“组织侵袭和转移”最显著相关。这些结果表明，与预后相关的关键miRNA-靶点相互作用与癌症转移高度相关。最后，我们观察到，在大多数TCGA癌症类型和独立验证集中，这些关键miRNA-靶点相互作用的组合能够区分预后良好和预后不良的患者，突出了它们在癌症转移中的作用。我们提供了一个名为miRNATarget的用户友好型数据库（可在http://biocc.hrbmu.edu.cn/miRNATar/免费获取），该数据库概述了16种癌症类型中与预后相关的关键miRNA-靶点相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/03af68569a74/oncotarget-08-109522-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/9524ff12f753/oncotarget-08-109522-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/05d3964cb500/oncotarget-08-109522-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/6302c75427bd/oncotarget-08-109522-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/9c9f3ac56580/oncotarget-08-109522-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/e4cd50d0572e/oncotarget-08-109522-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/03af68569a74/oncotarget-08-109522-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/9524ff12f753/oncotarget-08-109522-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/05d3964cb500/oncotarget-08-109522-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/6302c75427bd/oncotarget-08-109522-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/9c9f3ac56580/oncotarget-08-109522-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/e4cd50d0572e/oncotarget-08-109522-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53df/5752539/03af68569a74/oncotarget-08-109522-g006.jpg

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