Abstract
Prostate cancer is the leading cancer diagnosis in men, but only a subset of patients die from the disease. Understanding the molecular basis of aggressive prostate cancer remains elusive and few genomic biomarkers exist to guide clinical management. Long non-coding RNAs (lncRNAs) have emerged as a class of regulatory genes that play a role in several biological and disease processes, including cancer.
Recently, we identified SChLAP1, a novel, prognostic lncRNA expressed in a subset of prostate tumors. Mechanistically, SChLAP1 interacts with and inhibits genome-wide binding of the SWI/SNF nucleosome-remodeling complex. Additionally, SWI/SNF plays a key role in the epigenetic control of gene expression and has been shown to have tumor suppressive ability. Given the emerging role of SChLAP1 in the pathogenesis of aggressive prostate cancer and its interaction with the tumor suppressive SWI/SNF complex, exploring the detailed mechanism of action of SChLAP1 warranted further investigation.
To identify the regions of SChLAP1 necessary for its function, we created 250 base pair deletion constructs of SChLAP1 and measured RNA-enrichment following SWI/SNF pull-down as well as cell invasion using a Boyden chamber matrigel assay. To investigate whether SChLAP1 preferentially interacts with specific components of the SWI/SNF complex, we performed RNA immunoprecipitation assays using antibodies targeting various enzymatic subunits of SWI/SNF. SChLAP1 enrichment was measured by qPCR.
Our results indicate that there is a 250bp region of SChLAP1 that mediates its interaction with SWI/SNF and promotes an invasive phenotype. Furthermore, SChLAP1 shows binding specificity for certain SWI/SNF subunits. Future studies to elucidate the details of this interaction will provide a more comprehensive understanding of the biological and therapeutic consequences of SChLAP1 in prostate cancer progression.
Citation Format: Udit Singhal, Anirban Sahu, John R. Prensner, Qi Cao, Arul M. Chinnaiyan. SChLAP1 mediated epigenetic modifications in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2869. doi:10.1158/1538-7445.AM2015-2869
- ©2015 American Association for Cancer Research.