4.8 Article

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

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NATURE GENETICS
卷 45, 期 11, 页码 1392-+

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NATURE PORTFOLIO
DOI: 10.1038/ng.2771

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资金

  1. US National Institutes of Health (NIH) [P50CA69568]
  2. Early Detection Research Network grant [UO1 CA111275]
  3. US NIH grant [R01CA132874-01A1]
  4. US Department of Defense grant [PC100171]
  5. Doris Duke Charitable Foundation Clinical Scientist Award
  6. Prostate Cancer Foundation
  7. Howard Hughes Medical Institute
  8. US Department of Defense Predoctoral Fellowship [PC094290]

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Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority(1,2). The molecular basis for this clinical heterogeneity remains incompletely understood(3-5). 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.

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