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

2013; Nature Portfolio; Volume: 45; Issue: 11 Linguagem: Inglês

10.1038/ng.2771

1546-1718

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

interferon and immune responses

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.