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.
Highlights
Noncoding RNAs are found throughout the genome
We found that Hox transcript antisense intergenic RNA (HOTAIR) expression levels in colorectal cancer (CRC) tissues were higher than those in corresponding noncancerous tissues
As for clinicopathologic variables, HOTAIR expression levels were intimately linked to liver metastasis
Summary
Noncoding RNAs (ncRNA) are found throughout the genome. The functions of ncRNAs are only partially understood. Most long ncRNAs work with DNA-binding proteins, such as chromatinmodifying complexes, and epigenetically regulate the expression of multiple genes [1,2,3]. Hox transcript antisense intergenic RNA (HOTAIR) is a long ncRNA that was identified from a custom tilling array of the HOXC locus HOTAIR trimethylates histone H3 lysine-27 (H3K27me3) of Authors' Affiliations: 1Department of Surgery and 2Division of Cancer Genetics, Medical Institute of Bioregulation, and 3Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka; 4Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo; and 5Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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