HOTAIR

Summary

HOTAIR (HOX transcript antisense RNA, HGNC:33510) is a long non-coding RNA gene on chromosome 12q13.13.

This gene is located within the Homeobox C (HOXC) gene cluster on chromosome 12 and is co-expressed with the HOXC genes. It functions through an RNA product, which binds lysine specific demethylase 1 (LSD1) and Polycomb repressive complex 2 (PRC2), and serves as a scaffold to assemble these regulators at the HOXD gene cluster, thereby promoting epigenetic repression of HOXD. This gene is highly expressed in multiple tumors. Alternatively spliced transcript variants have been identified.

Source: NCBI Gene 100124700 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33510
Approved symbol	HOTAIR
Name	HOX transcript antisense RNA
Location	12q13.13
Locus type	RNA, long non-coding
Status	Approved
Aliases	HOXC-AS4, HOXC11-AS1, NCRNA00072
Ensembl gene	ENSG00000228630
Ensembl biotype	lncRNA
OMIM	611400
Entrez	100124700
RNAcentral	URS00026A23F2 — lncRNA, 2273 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 lncRNA

ENST00000424518, ENST00000425595, ENST00000439545, ENST00000453875, ENST00000455246, ENST00000698798, ENST00000710355, ENST00000717832, ENST00000717833, ENST00000717834, ENST00000717835, ENST00000717836, ENST00000774202, ENST00000774203

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000424518 — 7 exons

Exon	Start	End
ENSE00001595939	53962312	53964124
ENSE00001651059	53966276	53966377
ENSE00001652604	53967269	53967394
ENSE00001660281	53964231	53964283
ENSE00001700275	53974898	53974954
ENSE00001765623	53968617	53968756
ENSE00001794162	53965964	53966087

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 94.20.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4402 / max 55.0487, expressed in 118 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131281	0.1792	72
131283	0.1398	66
131282	0.0541	30
131279	0.0465	24
131284	0.0138	1
131280	0.0068	2

Top tissues by expression

213 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.20	gold quality
calcaneal tendon	UBERON:0003701	89.28	gold quality
popliteal artery	UBERON:0002250	88.12	gold quality
tibial artery	UBERON:0007610	88.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.23	gold quality
aorta	UBERON:0000947	82.58	gold quality
skin of leg	UBERON:0001511	77.45	gold quality
saphenous vein	UBERON:0007318	74.94	gold quality
zone of skin	UBERON:0000014	73.94	gold quality
right testis	UBERON:0004534	73.27	gold quality
skin of abdomen	UBERON:0001416	72.05	gold quality
tendon	UBERON:0000043	71.52	gold quality
sural nerve	UBERON:0015488	71.36	gold quality
left testis	UBERON:0004533	71.26	gold quality
testis	UBERON:0000473	69.67	gold quality
body of uterus	UBERON:0009853	67.70	gold quality
subcutaneous adipose tissue	UBERON:0002190	67.24	gold quality
muscle of leg	UBERON:0001383	66.72	gold quality
skin of hip	UBERON:0001554	66.51	gold quality
gastrocnemius	UBERON:0001388	66.19	gold quality
smooth muscle tissue	UBERON:0001135	63.59	gold quality
metanephros cortex	UBERON:0010533	61.14	gold quality
urethra	UBERON:0000057	58.76	silver quality
urinary bladder	UBERON:0001255	58.41	gold quality
cortex of kidney	UBERON:0001225	57.84	gold quality
lymph node	UBERON:0000029	57.74	gold quality
adipose tissue	UBERON:0001013	57.74	gold quality
myometrium	UBERON:0001296	57.63	gold quality
upper arm skin	UBERON:0004263	57.16	gold quality
monocyte	CL:0000576	57.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1

Literature-anchored findings (GeneRIF, showing 40)

• The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. (PMID:20393566)
• findings show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes; A 5’ domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3’ domain of HOTAIR binds the LSD1/CoREST/REST complex (PMID:20616235)
• HOTAIR expression is associated with a genome-wide reprogramming of PRC2 function not only in breast cancer but also in colorectal cancer, where upregulation of this long noncoding RNA may be a critical element in metastatic progression. (PMID:21862635)
• overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. (PMID:22258453)
• HOTAIR lincRNA might be a potential biomarker for the existence of lymph node metastasis in hepatocellular carcinoma. (PMID:22289527)
• HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. (PMID:22614017)
• intergenic DNA methylation may have important biologic relevance in regulating HOTAIR expression (PMID:23124417)
• HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. (PMID:23141928)
• HOTAIR expression is associated with hepatocellular carcinoma progression. (PMID:23292722)
• Estradiol induced transcription of antisense transcript HOTAIR which is coordinated via estrogen receptors and estrogen receptor coregulators, and this mechanism of HOTAIR overexpression potentially contributes towards breast cancer progression. (PMID:23375982)
• study demonstrates the 2 well-studied regulatory long non-coding RNAs HOTAIR and XIST are targets of site-specific cytosine methylation (PMID:23595112)
• Findings indicate that tumor-promoting Col-1 up-regulates the expression of HOTAIR in NSCLC cells. (PMID:23668363)
• HOTAIR is a potential biomarker for esophageal squamous cell carcinoma (ESCC) prognosis, and the dysregulation of HOTAIR may play an important role in ESCC progression. (PMID:23717443)
• Results indicate the expression of HOTAIR enhanced the aggressive behavior of non-small cell lung cancer (NSCLC) cells. (PMID:23743197)
• HOTAIR is overexpressed in metastatic tissue, which is associated with the ability of HOTAIR to promote melanoma cell motility and invasion. (PMID:23862139)
• A potential cooperative expression between HOTAIR and SUZ12 genes in gastric adenocarcinoma tissues is deduced. (PMID:23888369)
• The levels of plasma lncRNAs, H19, HOX antisense intergenic RNA (HOTAIR), and metastasis associated lung adenocarcinoma transcript-1 (MALAT1), were analyzed in patients with gastric cancer (GC) and healthy controls. (PMID:23898077)
• Data analysis suggested that HOTAIR-mediated gene regulation has a critical role in ESCC progression. (PMID:24022190)
• Data suggest that the role of Hotair in tumorigenesis occurs through EMT triggering and stemness acquisition. (PMID:24022994)
• The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. (PMID:24103700)
• HOTAIR directly decreased WIF-1 expression by promoting its histone H3K27 methylation in the promoter region and then activated the Wnt/beta-catenin signaling pathway. (PMID:24118380)
• In vitro assays of the esophageal squamous cell carcinoma cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. (PMID:24151120)
• upregulation of HOTAIR contributes to the cisplatin resistance of lung adenocarcinoma cells, at least in part, through the regulation of p21 expression. (PMID:24155936)
• HOTAIR overexpression is associated with mesenchymal glioma. (PMID:24203894)
• Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer. (PMID:24258260)
• We observed a significant association between HOTAIR expression and the endometrial carcinoma grade (p<0.05) and lymph node metastasis (p<0.05). (PMID:24285342)
• EZH2-EED is necessary and sufficient for binding to the lncRNA HOTAIR. (PMID:24320048)
• a role for HOTAIR, as a platform for protein ubiquitination (PMID:24326307)
• bisphenol-A and diethylstilbestrol exposure alters the epigenetic programming of the HOTAIR promoters leading to its endocrine disruption in vitro and in vivo. (PMID:24533973)
• High HOTAIR long non-coding RNA expression is associated with colorectal cancer. (PMID:24583926)
• Our results suggest that HOTAIR has an oncogenic role in SCLC and could be a prognostic biomarker and therapeutic target (PMID:24591352)
• Data suggest that HOTAIR plays a vital role in EOC metastasis. (PMID:24662839)
• Data indicate that long non-coding RNA HOTAIR is functionally related to RNA binding motif protein 38 (RBM38). (PMID:24663081)
• PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid arthritis. (PMID:24722995)
• High HOTAIR expression is associated with endometrial carcinoma. (PMID:24758900)
• HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. (PMID:24775712)
• A novel intronic HOTAIR enhancer locating between +1719bp and +2353bp from the transcriptional start site regulates gene expression in esophageal squamous cell carcinoma. (PMID:24788237)
• Results show that HOTAIR is mechanoresponsive and repressed by WNT b-CATENIN signaling providing evidence that HOTAIR is involved in aortic valve calcification. (PMID:24788418)
• study showed that HOTAIR lncRNA expression is up-regulated in colon cancer tissues and correlated with invaded lymph nodes. (PMID:24840737)
• HOTAIR expression is correlated with the migration of renal cell carcinoma cells, and HOTAIR may be involved in the curcumin-induced inhibition of renal cell carcinoma metastasis. (PMID:24935377)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.