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

  • Nat Genet. 2013 Nov;45(11):1392-8. doi: 10.1038/ng.2771.
John R Prensner  1 ,  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 Cao ,  Xiaoju Wang ,  Benjamin Chandler ,  Wei Yan ,  Javed Siddiqui ,  Lakshmi P Kunju ,  Saravana M Dhanasekaran ,  Kenneth J Pienta ,  Felix Y Feng ,  Arul M Chinnaiyan
Affiliations
  • 1. 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2].
PMID: 24076601 DOI: 10.1038/ng.2771
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.