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

Abstract

Arul Chinnaiyan and colleagues report that the long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers and predicts poor outcome. Mechanistically, they show that SChLAP1 promotes invasiveness and metastasis and antagonizes the functions of the SWI/SNF chromatin-remodeling complex. Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority1,2. The molecular basis for this clinical heterogeneity remains incompletely understood3,4,5. 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.