The lncRNA SChLAP1 is overexpressed in some prostate cancers and is predictive of poor outcome.

  • Major finding: The lncRNA SChLAP1 is overexpressed in some prostate cancers and is predictive of poor outcome.

  • Mechanism: SChLAP1 antagonizes gene regulation by the SWI/SNF complex by attenuating its genomic binding.

  • Impact: Cancer-associated lncRNAs can antagonize chromatin remodeling complex activity.

The molecular characteristics that distinguish high-risk, aggressive prostate cancers from indolent tumors are not well understood. Prensner and colleagues identified a long noncoding RNA (lncRNA), second chromosome locus associated with prostate-1 (SChLAP1), that was overexpressed in approximately 25% of prostate cancer samples, particularly in metastatic cancers. SChLAP1 expression was strongly correlated with higher Gleason scores and was a robust single-gene predictor of biochemical recurrence, clinical progression, and prostate cancer–specific mortality in patients initially diagnosed with localized prostate cancer. SChLAP1 knockdown significantly reduced prostate cancer cell proliferation and invasion in vitro and led to a marked reduction in invasion, intravasation, and metastatic seeding in vivo, providing support for a role of this lncRNA in prostate cancer aggressiveness. Genes deregulated upon SChLAP1 knockdown were enriched for those regulated by the SWI/SNF nucleosome remodeling complex, but knockdown of SChLAP1 had the opposite effect on these genes as knockdown of the essential SWI/SNF subunit SNF5, suggesting an antagonistic relationship that would be consistent with an oncogenic role of SChLAP1 and the known tumor-suppressive role of SWI/SNF complex subunits. SChLAP1 did not affect SNF5 expression, but RNA immunoprecipitation assays showed that endogenous SChLAP1 selectively interacted with SNF5, raising the possibility that SChLAP1 directly interferes with SWI/SNF activity. Indeed, SChLAP1 overexpression strongly reduced SNF5 genomic binding and led to deregulation of a subset of genes normally occupied by SNF5 near their transcription start sites. Unlike other lncRNAs, which have been found to facilitate the binding and activity of epigenetic regulators, these findings suggest that SChLAP1 may promote prostate cancer aggressiveness by antagonizing genomic binding and gene regulation by the SWI/SNF complex.

Prensner JR, Iyer MK, Sahu A, Asangani IA, Cao Q, Patel L, et al. The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet 2013 Sept 29 [Epub ahead of print].

Note: Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.

©2013 American Association for Cancer Research.
2013