Genome-wide profiling of EZH2-interacting RNAs reveals lncRNA MALAT1 inhibiting PCDH10 by recruiting PRC2 in metastatic gastric cancer cells. Genome-wide profiling of EZH2-interacting RNAs reveals lncRNA MALAT1 inhibiting PCDH10 by recruiting PRC2 in metastatic gastric cancer cells

Polycomb protein complexes are critical for stem cell renewal and tumorigenesis. Some components of Polycomb repressive complex 2 (PRC2) have been frequently found to be overexpressed in a variety of human cancers and contribute to tumor initiation and development partially by transcriptional silencing of tumor suppressor genes. However, the exact underlying mechanisms still remain elusive. To further characterize PRC2-directed transcriptome and explore its implication in tumorigenesis, here we performed a genome-wide profiling of EZH2-associated, a key component of PRC2, transcriptome in human gastric cancer cell lines by RNA immunoprecipitation sequencing (RIP-seq). We observed that the EZH2-interacting transcripts are distributed in protein-coding, intergenic, intronic and promoter regions and transcribed from both strands. Many transcripts are originated from cancer-related loci and transcribed from active promoters. Particularly, we demonstrated that EZH2-associated lncRNA MALAT1 tethers EZH2 to PCDH10 promoter for its transcriptional repression and contributes to gastric cellular invasion and migration.