Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers

Ryunosuke Kogo, Teppei Shimamura, Koshi Mimori, Kohichi Kawahara, Seiya Imoto, Tomoya Sudo, Fumiaki Tanaka, Kohei Shibata, Akira Suzuki, Shizuo Komune, Satoru Miyano, Masaki Mori

Research output: Contribution to journalArticlepeer-review

1129 Citations (Scopus)

Abstract

The functional impact of recently discovered long noncoding RNAs (ncRNAs) in human cancer remains to be clarified. One long ncRNA which has attracted attention is the Hox transcript antisense intergenic RNA termed HOTAIR, a long ncRNA expressed from the developmental HOXC locus located on chromosome 12q13.13. In cooperation with Polycomb complex PRC2, the HOTAIR long ncRNA is reported to reprogram chromatin organization and promote breast cancer metastasis. In this study, we examined the status and function of HOTAIR in patients with stage IV colorectal cancer (CRC) who have liver metastases and a poor prognosis. HOTAIR expression levels were higher in cancerous tissues than in corresponding noncancerous tissues and high HOTAIR expression correlated tightly with the presence of liver metastasis. Moreover, patients with high HOTAIR expression had a relatively poorer prognosis. In a subset of 32 CRC specimens, gene set enrichment analysis using cDNA array data revealed a close correlation between expression of HOTAIR and members of the PRC2 complex (SUZ12, EZH2, and H3K27me3). Our findings suggest that HOTAIR expression is associated with a genome-wide reprogramming of PRC2 function not only in breast cancer but also in CRC, where upregulation of this long ncRNA may be a critical element in metastatic progression.

Original languageEnglish
Pages (from-to)6320-6326
Number of pages7
JournalCancer Research
Volume71
Issue number20
DOIs
Publication statusPublished - Oct 15 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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