HOTTIP

Summary

HOTTIP (HOXA distal transcript antisense RNA, HGNC:37461) is a long non-coding RNA gene on chromosome 7p15.2.

This gene produces a long RNA in antisense to the HOXA gene cluster. This transcript may regulate expression of HOXA genes in cis. This gene is upregulated in tumors and is implicated in the promotion of cell proliferation.

Source: NCBI Gene 100316868 — 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:37461
Approved symbol	HOTTIP
Name	HOXA distal transcript antisense RNA
Location	7p15.2
Locus type	RNA, long non-coding
Status	Approved
Aliases	HOXA-AS6, RP1-170O19.3, HOXA13-AS1
Ensembl gene	ENSG00000243766
Ensembl biotype	lncRNA
OMIM	614060
Entrez	100316868
RNAcentral	URS000075E1E7 — lncRNA, 4665 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 lncRNA

ENST00000421733, ENST00000472494, ENST00000521028, ENST00000605136, ENST00000814985, ENST00000814986, ENST00000814987

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000421733 — 2 exons

Exon	Start	End
ENSE00002431848	27200623	27201236
ENSE00002478801	27198575	27198741

Expression profiles

Bgee: expression breadth broad, 58 present calls, max score 85.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0553 / max 9.4200, expressed in 26 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77816	0.0553	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	85.18	gold quality
mucosa of transverse colon	UBERON:0004991	84.10	gold quality
transverse colon	UBERON:0001157	78.41	gold quality
endocervix	UBERON:0000458	78.37	gold quality
prostate gland	UBERON:0002367	77.29	gold quality
ectocervix	UBERON:0012249	76.78	gold quality
uterine cervix	UBERON:0000002	75.33	gold quality
colonic epithelium	UBERON:0000397	74.56	gold quality
vagina	UBERON:0000996	73.53	gold quality
placenta	UBERON:0001987	73.33	gold quality
left ovary	UBERON:0002119	70.40	gold quality
colon	UBERON:0001155	68.93	gold quality
intestine	UBERON:0000160	68.90	gold quality
urinary bladder	UBERON:0001255	67.54	gold quality
fundus of stomach	UBERON:0001160	62.25	gold quality
multicellular organism	UBERON:0000468	58.43	gold quality
ovary	UBERON:0000992	57.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	56.91	gold quality
skeletal muscle tissue	UBERON:0001134	55.77	gold quality
liver	UBERON:0002107	54.95	gold quality
smooth muscle tissue	UBERON:0001135	54.80	gold quality
myometrium	UBERON:0001296	53.44	gold quality
prefrontal cortex	UBERON:0000451	51.54	silver quality
calcaneal tendon	UBERON:0003701	51.44	silver quality
lymph node	UBERON:0000029	50.89	gold quality
blood	UBERON:0000178	50.74	silver quality
body of uterus	UBERON:0009853	50.65	gold quality
muscle of leg	UBERON:0001383	48.73	gold quality
gastrocnemius	UBERON:0001388	47.14	silver quality
heart	UBERON:0000948	46.44	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.12

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• miR-101 and HOTTIP are involved in cartilage regulation. (PMID:24018042)
• Our study highlights the key role of HOTTIP and HOXA13 in hepatocellular carcinoma development. (PMID:24114970)
• HOTTIP is a novel oncogenic lncRNA, which is negatively regulated by miR-125b. Overexpression of HOTTIP contributes to hepatocarcinogenesis by regulating the expression of its neighbouring protein-coding genes. (PMID:25424744)
• HOTTIP/HOXA13 axis is a potential therapeutic target and molecular biomarker for pancreatic ductal adenocarcinoma. (PMID:25889214)
• The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation, survival and migration. (PMID:25912306)
• study demonstrates that aberrant reduction of HOTTIP and HOXA13, which have a bidirectional regulatory loop, may play an important role in the pathogenesis of HSCR (PMID:26043692)
• In conclusion, increased lncRNA HOTTIP expression may be serve as an unfavorable prognosis predictor for tongue squamous cell carcinoma patients (PMID:26058875)
• lncRNA HOTTIP plays a critical role in osteosarcoma progression and could represent a novel prognostic marker (PMID:26617868)
• lncRNA HOTTIP overexpression maybe serves as an unfavorable prognosis predictor for colorectal cancer patients. (PMID:26617875)
• High HOTTIP expression is associated with colorectal cancer. (PMID:26678886)
• Down-regulation of HOTTIP and HOXA13 was associated with cell growth and cell cycle, and exerts tumor-suppressive functions in the genesis and progression of prostate cancer, providing a potential attractive therapeutic approach for this malignancy. (PMID:27064878)
• HOTTIP was upregulated in gastric cancer cell lines. Knockdown of HOTTIP in gastric cancer cells inhibited cell proliferation, migration and invasion. expression levels of HOTTIP and HOXA13 were both higher in gastric cancer which was poorly differentiated, at advanced TNM stages and exhibited lymph node-metastasis. (PMID:27108607)
• Knockdown of HoxA13 caused the downregulation of long non-coding RNA HOTTIP and insulin growth factor-binding protein 3 (IGFBP-3) genes, indicating that both were targets of HoxA13. (PMID:27144338)
• Results show that HOTTIP expression is down-regulated in glioma tissues and glioma cell lines, and that HOTTIP could directly bind to BRE gene and down-regulate its expression. Also, the study demonstrates that overexpression of HOTTIP promotes cell apoptosis and inhibits cell growth of glioma cell lines. (PMID:27733185)
• Our findings provide an approach to mimic in vitro a key early stage in human hematopoiesis for the generation of AGM-derived hematopoietic lineages from hESCs. (PMID:27748754)
• Data suggest that long noncoding RNA HOTTIP (HOTTIP) could be an oncogene for esophageal squamous cell carcinoma (ESCC), and may be served as a candidate target for therapies in ESCC. (PMID:27806322)
• this meta-analysis demonstrated that the higher expression level of HOTTIP is correlated with positive lymph node metastasis and poor overall survival in different types of cancer (PMID:27806342)
• Review/Meta-analysis: high HOTTIP expression is an unfavorable prognosis predictor for breast cancer patients. (PMID:28036281)
• HOTTIP was an independent prognostic factor for cancers, and high-expression HOTTIP predicts poor prognosis. (PMID:28164688)
• short isoform (p52) of a transcriptional co-activator-PC4 and SF2 interacting protein (Psip1), which is known to be involved in linking transcription to RNA processing, specifically regulates the expression of the lncRNA Hottip-located at the 5’ end of the Hoxa locus (PMID:28384324)
• Findings indicated that HOTTIP modulated HOXA13 at both the transcriptional and posttranscriptional levels in ESCC cells. (PMID:28534516)
• Findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. (PMID:28782268)
• HOTTIP rs1859168 A > C showed to be significantly associated with a reduced pancreatic cancer risk in Chinese population. (PMID:28818070)
• HIF-1alpha/HOTTIP/miR-101/ZEB1 axis plays essential role in hypoxia-induced epithelial-mesenchymal transition and metastasis of glioma. (PMID:28886531)
• HOTTIP/WDR5/HOXA9/Wnt axis contributes to pancreatic tumor stem cell stemness. (PMID:28947139)
• HOTTIP was upregulated in HCC. A statistically significant higher expression of HOTTIP was found in TNM (III +), age (>/=60), sex (male), race (white) and cirrhosis (no) compared to the control groups (P<0.05). (PMID:29039502)
• These results suggested that HOTTIP might manipulate the endothelial cell proliferation and migration via activation of the Wnt/beta-catenin pathway. (PMID:29058802)
• OTTIP can promote the progression of lung adenocarcinoma, and the formation of lung adenocarcinoma resistance regulated by the protein kinase B (AKT) signaling pathway (PMID:29272003)
• Knockdown of HOTTIP inhibits cell proliferation, cell migration and induces cell apoptosis in colorectal cancer cells. (PMID:29274585)
• Increased long noncoding RNA HomeoboxA transcript at the distal tip (HOTTIP) expression was associated with poor prognosis independent of KRAS mutation. (PMID:29329159)
• HOTTIP increased the expression of anti-apoptotic factor BCL-2, another important target gene of miR-216a, and jointly enhanced chemoresistance of small cell lung cancer by regulating BCL-2. (PMID:29367594)
• we uncovered a novel potential regulatory mechanism between HOTTIP and one of its physical HOXA clusters, HOXA11. Hence, HOTTIP may mediate, at least partly, HOXA11 expression involved in cell growth, migration, and apoptosis of breast cancer MCF-7 cells. (PMID:29415429)
• High HOTTIP expression is associated with papillary thyroid carcinoma cell proliferation, invasion and migration. (PMID:29474928)
• HOTTIP cooperates with CTCF to coordinate HOXA gene expression. (PMID:29698677)
• HOTTIP was up-regulated in the primary prostate cancer tissues with lymph node metastasis. HOTTIP negatively regulates miR-216a-5p expression in prostate cancer. (PMID:29884766)
• HOTTIP was lowly expressed in preeclampsia and was able to suppress the progression of preeclampsia. (PMID:29917176)
• HOTTIP plays an oncogenic role in renal cell carcinoma and is associated with unfavorable phenotypes. (PMID:30021349)
• HOTTIP remarkably promotes proliferative and invasive abilities, but inhibits cell apoptosis of mammary cancer cells via PI3K/AKT pathway. (PMID:30024606)
• Study demonstrated that HOTTIP expression was significantly upregulated in renal cell carcinoma (RCC) and was associated with a shorter survival. The inhibition of HOTTIP suppressed cell proliferation, migration and invasion in RCC. In addition, IFG-2 was found to be a direct target gene of HOTTIP. HOTTIP directly bound to miR-615 and effectively acted as a sponge for miR-615 to modulate the suppression of IFG-2. (PMID:30226576)
• HOTTIP regulates colorectal cancer cell metastasis partly through the downregulation of tumor suppressor DKK1 expression (PMID:30229808)

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.