The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex.
Abstract
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.
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Authors
- Asangani IA
- Bedenis R
- Cao Q
- Cao X
- Chandler B
- Chen W
- Chinnaiyan AM
- Davicioni E
- Dhanasekaran SM
- Erho N
- Feng FY
- Ghadessi M
- Han S
- Iyer MK
- Jenkins RB
- Jing X
- Kunju LP
- Ma T
- Malik R
- McGregor N
- Patel L
- Pienta KJ
- Prensner JR
- Sahu A
- Siddiqui J
- Triche TJ
- Vergara IA
- Wang X
- Yan W