title: Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers.
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.
authors.affiliation: Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Kogo
authors.forename: Teppei
authors.initials: T
authors.lastname: Shimamura
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Kohichi
authors.initials: K
authors.lastname: Kawahara
authors.forename: Seiya
authors.initials: S
authors.lastname: Imoto
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Kohei
authors.initials: K
authors.lastname: Shibata
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Komune
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000556:secondary*; D042002:Chromatin Assembly and Disassembly; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D063146:Polycomb-Group Proteins; D011379:Prognosis; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C561566:HOTAIR long untranslated RNA, human; D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins