Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

被引：260

作者：

Chiu, Hua-Sheng ^{[1
]}

Somvanshi, Sonal ^{[1
]}

Patel, Ektaben ^{[1
]}

Chen, Ting-Wen ^{[2
]}

Singh, Vivek P. ^{[3
]}

Zorman, Barry ^{[1
]}

Patil, Sagar L. ^{[4
]}

Pan, Yinghong ^{[4
]}

Chatterjee, Sujash S. ^{[4
]}

Sood, Anil K. ^{[5
]}

Gunaratne, Preethi H. ^{[4
]}

Sumazin, Pavel ^{[1
]}

机构：

[1] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA

[2] Chang Gung Univ, Bioinformat Ctr, Mol Med Res Ctr, Taoyuan, Taiwan

[3] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA

[4] Univ Houston, Dept Biol & Biochem, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Div Surg, Houston, TX 77030 USA

来源：

CELL REPORTS | 2018年 / 23卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

LONG NONCODING RNAS; TRANSCRIPTION FACTOR; CELL-PROLIFERATION; BINDING SITES; EXPRESSION; LANDSCAPE; DATABASE; IDENTIFICATION; ENCYCLOPEDIA; VALIDATION;

D O I：

10.1016/j.celrep.2018.03.064

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco- lncRNAs) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts.

引用

页码：297 / +

页数：28

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