The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex

被引：652

作者：

Prensner, John R. ^{[1
]}

Iyer, Matthew K. ^{[1
,2
]}

Sahu, Anirban ^{[1
]}

Asangani, Irfan A. ^{[1
]}

Cao, Qi ^{[1
]}

Patel, Lalit ^{[1
,3
]}

Vergara, Ismael A. ^{[4
]}

Davicioni, Elai ^{[4
]}

Erho, Nicholas ^{[4
]}

Ghadessi, Mercedeh ^{[4
]}

Jenkins, Robert B. ^{[5
]}

Triche, Timothy J. ^{[4
]}

Malik, Rohit ^{[1
]}

Bedenis, Rachel ^{[3
]}

McGregor, Natalie ^{[3
]}

Ma, Teng ^{[6
]}

Chen, Wei ^{[6
]}

Han, Sumin ^{[6
]}

Jing, Xiaojun ^{[1
]}

Cao, Xuhong ^{[1
]}

Wang, Xiaoju ^{[1
]}

Chandler, Benjamin ^{[1
]}

Yan, Wei ^{[1
]}

Siddiqui, Javed ^{[1
]}

Kunju, Lakshmi P. ^{[1
,7
,8
]}

Dhanasekaran, Saravana M. ^{[1
,7
]}

Pienta, Kenneth J. ^{[1
,3
]}

Feng, Felix Y. ^{[1
,6
,8
]}

Chinnaiyan, Arul M. ^{[1
,2
,7
,8
,9
]}

机构：

[1] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[4] GenomeDx Biosci Inc, Vancouver, BC, Canada

[5] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[6] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA

[7] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[8] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[9] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

来源：

NATURE GENETICS | 2013年 / 45卷 / 11期

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION ANALYSIS; CHROMATIN; REVEALS; PROGRESSION; SIGNATURES; MUTATIONS; DISCOVERY; POLYCOMB; NETWORKS; FUSIONS;

D O I：

10.1038/ng.2771

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority(1,2). The molecular basis for this clinical heterogeneity remains incompletely understood(3-5). Here we characterize a long noncoding RNA termed SChLAP1 (second chromosome locus associated with prostate-1; also called LINC00913) that is overexpressed in a subset of prostate cancers. SChLAP1 levels independently predict poor outcomes, including metastasis and prostate cancer-specific mortality. In vitro and in vivo gain-of-function and loss-of-function experiments indicate that SChLAP1 is critical for cancer cell invasiveness and metastasis. Mechanistically, SChLAP1 antagonizes the genome-wide localization and regulatory functions of the SWI/SNF chromatin-modifying complex. These results suggest that SChLAP1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.

引用

页码：1392 / +

页数：12

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