The Enhancer Landscape Involves A Core Noncoding Rna Protein Interaction Network For C-Myc Expression

Many long non-coding RNAs (lncRNAs) that regulate the capacity of cells to undergo oncogenic transformation still remain unknown. However, their involvement in chromatin organization has been an emerging principle in cancer epigenomics. This recent concept has been documented through recent studies of the gene -poor chromosomal region 8q24 surrounding the C-MYC locus to understand the mechanisms enforcing or suppressing tumor cell growth from C-MYC transcription levels. In light of such examples informing us of the DNA elements and the epigenomic composition that become integrated into molecular programs that regulate C-MYC , some lncRNAs in non-genic regions are considered landmarks that enforce chromatin state changes to accommodate C-MYC expression. Here, we use an integrative genomic and proteomic approach to gain insight of how an endogenously tagged lncRNA PCAT-1 utilizes the chromatin and biochemical context to shape C-MYC locus topology to promote tumor cell growth, survival and fitness. Our results now find that WDR74 forms an integrative hub involving recognition of the m7G cap of lncRNA transcripts along with, RNMT, RAM, BRD4, β catenin, EZH2 that assist in a program that enforce C-MYC transcription and stabilize transcripts through utilizing a comprehensive mixture of cis -acting DNA elements, lncRNAs and trans functioning transcriptional and RNA capping complexes for prostate tumor cell growth. Our results now place the lncRNA PCAT-1 and the novel interacting WD40 repeat protein WDR74 at the axis along with β catenin, BRD4 and EZH2, and additional RBPs as a non -canonical chromatin complex to shape the chromosomal topology that benefit prostate cancer cell growth. Citation Format: Fan Zhang, Won-min Song, SiDe Li, Vashisht Ajay, Francesca Aguilo, Anindya Bagchi, James A. Wohlschlegel, Bin Zhang, Martin Walsh. The enhancer landscape involves a core noncoding RNA protein interaction network for C-MYC expression. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr PR06.