HOTAIR

HOTAIR (for HOX transcript antisense RNA)[3] is a human gene located on chromosome 12. It is the first example of an RNA expressed on one chromosome that has been found to influence transcription on another chromosome.

HOTAIR
Identifiers
AliasesHOTAIR, HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072, HOX transcript antisense RNA
External IDsOMIM: 611400 GeneCards: HOTAIR
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q13.13Start53,962,308 bp[1]
End53,974,956 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

100124700

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Ensembl

ENSG00000228630

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UniProt

n/a

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)Chr 12: 53.96 – 53.97 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Gene and transcribed RNA product

The HOTAIR gene contains 6,232 bp and encodes 2.2 kb long noncoding RNA molecule, which controls gene expression. Its source DNA is located within a HOXC gene cluster. It is shuttled from chromosome 12 to chromosome 2 by the Suz-Twelve protein.[4]

Function

The 5′ end of HOTAIR interacts with a Polycomb-group protein Polycomb Repressive Complex 2 (PRC2) and as a result regulates chromatin state. It is required for gene-silencing of the HOXD locus by PRC2.[5][6] The 3′ end of HOTAIR interacts with the histone demethylase LSD1.[6]

It is an important factor in the epigenetic differentiation of skin over the surface of the body. Skin from various anatomical positions is distinct, e.g. the skin of the eyelid differs markedly from that on the sole of the foot.[5][7]

Clinical significance

HOTAIR is highly expressed in metastatic breast cancers. High levels of expression in primary breast tumours are a significant predictor of subsequent metastasis and death. This is partially due to HOTAIR-mediated overexpression of the HER2 oncogene through sequestration of miR-331-3p, which is a negative regulator of HER2 expression[8]. In cells, especially those that over express PRC2, the prevention of HOTAIR expression leads to a reduction in invasive potential of that cell. [9] It is also involved in esophageal squamous cell carcinoma.[10]

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References
  1. GRCh38: Ensembl release 89: ENSG00000228630 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Genecards entry on HOTAIR". Retrieved 20 July 2010.
  4. Petherick A (Aug 2008). "Genetics: The production line". Nature. 454 (7208): 1042–1045. doi:10.1038/4541042a. PMID 18756228.
  5. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (Jun 2007). "Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs". Cell. 129 (7): 1311–1323. doi:10.1016/j.cell.2007.05.022. PMC 2084369. PMID 17604720.
  6. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (Aug 2010). "Long noncoding RNA as modular scaffold of histone modification complexes". Science. 329 (5992): 689–693. doi:10.1126/science.1192002. PMC 2967777. PMID 20616235.
  7. Chuong CM (Jan 2003). "Homeobox genes, fetal wound healing, and skin regional specificity". The Journal of Investigative Dermatology. 120 (1): 9–11. doi:10.1046/j.1523-1747.2003.00002.x. PMC 4383243. PMID 12535191.
  8. Liu, Xiang-hua; Sun, Ming; Nie, Feng-qi; Ge, Ying-bin; Zhang, Er-bao; Yin, Dan-dan; Kong, Rong; Xia, Rui; Lu, Kai-hua (2014-04-28). "Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer". Molecular Cancer. 13: 92. doi:10.1186/1476-4598-13-92. ISSN 1476-4598. PMC 4021402. PMID 24775712.
  9. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (Apr 2010). "Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis". Nature. 464 (7291): 1071–1076. doi:10.1038/nature08975. PMC 3049919. PMID 20393566.
  10. Chen FJ, Sun M, Li SQ, Wu QQ, Ji L, Liu ZL, Zhou GZ, Cao G, Jin L, Xie HW, Wang CM, Lv J, De W, Wu M, Cao XF (Nov 2013). "Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis". Molecular Carcinogenesis. 52 (11): 908–915. doi:10.1002/mc.21944. PMID 24151120.

Further reading
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