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

JR Prensner, MK Iyer, A Sahu, IA Asangani, Q Cao… - Nature …, 2013 - nature.com
Nature genetics, 2013nature.com
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 …
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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