HOTAIR epigenetically silence gene expression at many sites across the genome by recruitment of chromatin modifying complexes and the abnormal expression of HOTAIR is highly correlated with the development of many kinds of human cancers.
Approved symbol: HOTAIR
Approved name: HOX transcript antisense RNA
HGNC ID: HGNC:33510
Previous names: HOX transcript antisense RNA (non-protein coding)
Alias symbols: HOXC-AS4; HOXC11-AS1; NCRNA00072
Alias names: HOXC cluster antisense RNA 4 (non-protein coding); non-protein coding RNA 72
RefSeq ID: NR_003716
LncBook ID: HSALNT0289004
2.2 kb; spliced, polyadenylated and comprised of 6 exons in humans .
Transcribed from the HOXC locus from a position intergenic and antisense to the flanking HOXC11 and HOXC12 genes .
Some HOTAIR transcripts localise to the nucleus .
Transcript found to be quite unstable with a half-life >4 hr in human Hela cells.
Originally identified as silencing the HoxD locus but has since been found to epigenetic silence gene expression at many sites across the genome by recruitment of PRC2 and LSD1/CoREST/REST repressive chromatin modifying complexes .
HOTAIR has been suggested to function at the chromatin level by interacting with chromatin modifying protein complexes . It has been reported that HOTAIR expression is correlated with SUZ12 expression level and therefore may affect the epigenetic state of cancer tissues. HOTAIR acts as a scaffold for protein complexes. A 5' domain binds PRC2 while a 3' domain binds LSD1. Oncogenic effects of HOTAIR upregulation were dependent on PRC2 .
Oncogene - regulates metastatic progression in many kinds of cancers . It is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells. There was a great upregulation of HOTAIR in Esophageal squamous cell carcinoma (ESCC) compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro. Knockdown of HOTAIR decreased prostate cancer (PCa) cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest . High HOTAIR expression tightly correlated with the presence of liver metastasis and associated with poor prognosis . The aberrant expression of HOTAIR was associated with TNM staging and lymph node metastasis of gastric tumors. Reduced expression of HOTAIR in KATO III suppressed peritoneal dissemination suggest that HOTAIR plays a pivotal role in the development of gastric cancer.
Deletion of the HoxC cluster containing the cognate Hotair transcript in mouse showed little phenotypic effect, with little change in the expression on levels of H3K27me3 coverage in corresponding human HOTAIR Hoxd target genes .
HOTAIR acts as an inducer of ubiquitin-mediated proteolysis on post-translational function. HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. HOTAIR levels are highly upregulated in senescent cells, causing rapid decay of targets Ataxin-1 and Snurportin-1, and preventing premature senescence.
Expressed in posterior and distal fibroblasts .
In situ hybridization analysis of the mouse cognate RNA (mHotair) showed expression similar to Hoxc11, with distinct levels in parts of the proximal hindlimbs, genital bud and tail in embryos at E11.5, as well as in in posterior part of the hindlimb and genital bud at E12.5 .
It is up-regulated in breast cancer , colorectal cancer (CRC) , Esophageal squamous cell carcinoma (ESCC) , ovarian cancer , gastric adenocarcinoma samples ,Non-small-cell lung carcinoma (NSCLC) , laryngeal squamous cell cancer (LSCC) ,cisplatin-resistant A549/DDP cells .
The mouse EST (AK035706) homologous to human HOTAIR is comprised of two exons only, with the second half of the first exon showing similarity to exon 4 of HOTAIR, whereas the second exon is homologous to exon 6 of HOTAIR . This may underlie differences in function since the first three exons of HOTAIR (absent from mHotair) contain binding sites for EZH2, while the 3' extremity of human HOTAIR that interact with LSD1 is part of the least conserved DNA sequence within mHotair exon 2 .
HOTAIR is transcriptionally induced by estradiol (E2). Similar to protein-coding gene transcription, E2-induced transcription of antisense transcript HOTAIR is coordinated via ERs and ER coregulators, and this mechanism of HOTAIR overexpression potentially contributes towards breast cancer progression. The long non-coding RNA HOTAIR has been reported to be a poor prognostic biomarker in a variety of malignant tumors.
LncRNA profiling showed that HOTAIR was highly regulated by genistein and its expression was higher in castration-resistant PCa cell lines than in normal prostate cells. miR-34a was also up-regulated by genistein and may directly target HOTAIR in both PC3 and DU145 PCa cells.
There is site-specific cytosine methylation in the lncRNA HOTAIR. Methylation of C1683 may affect the ability of HOTAIR to interact with LSD1.
B-cell neoplasms,breast cancer,cervical cancer,colon cancer,colorectal cancer,endometrial cancer,gastric cancer,hepatocelluar carcinoma,laryngeal squamous cell carcinoma,liver cancer,lung adenocarcinoma,nasopharyngeal carcinoma,non-small cell lung cancer,oesophageal squamous cell carcinoma,oral squamous cell carcinoma,pancreas cancer,rheumatoid arthritis,small cell lung cancer
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Labs working on this lncRNA
Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, Maryland 21224, USA .
Bioinformatics Section, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China .
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, Japan .
School of Life Sciences, Federal Institute of Technology, Lausanne, Switzerland .
The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA .
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan .
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA .
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