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Prensner, John R; Iyer, Matthew K; Sahu, Anirban; Asangani, Irfan A; Cao, Qi; Patel, Lalit; Vergara, Ismael A; Davicioni, Elai; Erho, Nicholas; Ghadessi, Mercedeh; Jenkins, Robert B; Triche, Timothy J; Malik, Rohit; Bedenis, Rachel; McGregor, Natalie; Ma, Teng; Chen, Wei; Han, Sumin; Jing, Xiaojun; Cao, Xuhong; Wang, Xiaoju; Chandler, Benjamin; Yan, Wei; Siddiqui, Javed; Kunju, Lakshmi P; Dhanasekaran, Saravana M; Pienta, Kenneth J; Feng, Felix Y; Chinnaiyan, Arul M
Nature genetics, 11/2013, Volume: 45, Issue: 11Journal Article
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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