MALAT1 long ncRNA promotes gastric cancer metastasis by suppressing PCDH10

Oncotarget. 2016 Mar 15;7(11):12693-703. doi: 10.18632/oncotarget.7281.

Abstract

EZH2, the catalytic component of polycomb repressive complex 2 (PRC2), is frequently overexpressed in human cancers and contributes to tumor initiation and progression, in part through transcriptional silencing of tumor suppressor genes. A number of noncoding RNAs (ncRNAs) recruit EZH2 to specific chromatin loci, where they modulate gene expression. Here, we used RNA immunoprecipitation sequencing (RIP-seq) to profile EZH2-associated transcripts in human gastric cancer cell lines. We identified 8,256 transcripts, including both noncoding and coding transcripts, some of which were derived from cancer-related loci. In particular, we found that long noncoding RNA (lncRNA) MALAT1 binds EZH2, suppresses the tumor suppressor PCDH10, and promotes gastric cellular migration and invasion. Our work thus provides a global view of the EZH2-associated transcriptome and offers new insight into the function of EZH2 in gastric tumorigenesis.

Keywords: EZH2; MALAT1; RIP-seq; gastric cancer; transcriptional silencing.

MeSH terms

  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Protocadherins
  • RNA, Long Noncoding / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*

Substances

  • Cadherins
  • MALAT1 long non-coding RNA, human
  • PCDH10 protein, human
  • Protocadherins
  • RNA, Long Noncoding
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein