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

John R. Prensner, Matthew K. Iyer, Anirban Sahu, Irfan A. Asangani, Qi Cao, Lalit 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 CaoXiaoju Wang, Benjamin Chandler, Wei Yan, Javed Siddiqui, Lakshmi P. Kunju, Saravana M. Dhanasekaran, Kenneth J. Pienta, Felix Y. Feng, Arul M. Chinnaiyan*

*Corresponding author for this work

Research output: Contribution to journalLetter

391 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1392-1403
Number of pages12
JournalNature Genetics
Volume45
Issue number11
DOIs
StatePublished - Nov 1 2013

ASJC Scopus subject areas

  • Genetics

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    Prensner, J. R., Iyer, M. K., Sahu, A., Asangani, I. A., Cao, Q., Patel, L., Vergara, I. A., Davicioni, E., Erho, N., Ghadessi, M., Jenkins, R. B., Triche, T. J., Malik, R., Bedenis, R., McGregor, N., Ma, T., Chen, W., Han, S., Jing, X., ... Chinnaiyan, A. M. (2013). The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nature Genetics, 45(11), 1392-1403. https://doi.org/10.1038/ng.2771