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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line, Tumor
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Cell Proliferation
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Chromosomal Proteins, Non-Histone / genetics*
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Chromosomal Proteins, Non-Histone / metabolism*
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DNA-Binding Proteins / genetics*
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Female
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Gene Expression Profiling
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Humans
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Male
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Mice
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Molecular Sequence Data
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Neoplasm Invasiveness / genetics
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Neoplasm Metastasis / genetics
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Promoter Regions, Genetic
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Prostatic Neoplasms / genetics*
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RNA Interference
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RNA, Long Noncoding / genetics*
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RNA, Small Interfering
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SMARCB1 Protein
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
Substances
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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RNA, Long Noncoding
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RNA, Small Interfering
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SMARCB1 Protein
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SMARCB1 protein, human
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SWI-SNF-B chromatin-remodeling complex
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Transcription Factors
Associated data
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GENBANK/JX117418
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GENBANK/JX117419
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GENBANK/JX117420
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GENBANK/JX117421
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GENBANK/JX117422
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GENBANK/JX117423
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GENBANK/JX117424