The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex.
Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. 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.
1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2].
John R
JR
Prensner
Matthew K
MK
Iyer
Anirban
A
Sahu
Irfan A
IA
Asangani
Qi
Q
Cao
Lalit
L
Patel
Ismael A
IA
Vergara
Elai
E
Davicioni
Nicholas
N
Erho
Mercedeh
M
Ghadessi
Robert B
RB
Jenkins
Timothy J
TJ
Triche
Rohit
R
Malik
Rachel
R
Bedenis
Natalie
N
McGregor
Teng
T
Ma
Wei
W
Chen
Sumin
S
Han
Xiaojun
X
Jing
Xuhong
X
Cao
Xiaoju
X
Wang
Benjamin
B
Chandler
Wei
W
Yan
Javed
J
Siddiqui
Lakshmi P
LP
Kunju
Saravana M
SM
Dhanasekaran
Kenneth J
KJ
Pienta
Felix Y
FY
Feng
Arul M
AM
Chinnaiyan
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors