HOTAIR; HOX transcript antisense RNA (12q13.13)

Gene Summary

Gene:HOTAIR; HOX transcript antisense RNA
Aliases: HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072
Summary:This gene is located within the Homeobox C (HOXC) gene cluster on chromosome 12 and is co-expressed with HOXC genes. It represses transcription of HOXD genes on chromosome 2 in trans. This gene is shuttled from chromosome 12 to chromosome 2 by a component of Polycomb Repressive Complex 2 (PRC2). This gene interacts with both PRC2 and lysine specific demethylase 1 (LSD1) complexes through its 5' and 3' domains, respectively, and serves as a scaffold to assemble PRC2 and LSD1 complexes to the HOXD gene cluster. It couples H3K27 methylation and H3K4 demethylation for epigenetic silencing of HOXD genes in multiple tissues. This gene is highly expressed in multiple tumors. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Feb 2013]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Updated:12 December, 2014

Cancer Overview

Research Indicators

Publications Per Year (1989-2014)
Graph generated 12 December 2014 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Survival Rate
  • RNA, Long Noncoding
  • Cell Proliferation
  • Chromatin Assembly and Disassembly
  • DNA Methylation
  • Tumor Markers
  • Xenograft Models
  • Breast Cancer
  • Neoplasm Grading
  • Transcription Factors
  • Messenger RNA
  • Risk Factors
  • Disease Progression
  • Follow-Up Studies
  • Neoplasm Invasiveness
  • Lung Cancer
  • Cell Movement
  • Case-Control Studies
  • Staging
  • Histones
  • Neoplasm Metastasis
  • Homeodomain Proteins
  • Mice, Inbred BALB C
  • Apoptosis
  • Gene Knockdown Techniques
  • RNA, Untranslated
  • Cancer Gene Expression Regulation
  • Chromosome 12
  • Squamous Cell Carcinoma
  • Up-Regulation
  • Esophageal Cancer
  • MicroRNAs
  • Repressor Proteins
  • RNA Interference
  • Lymphatic Metastasis
  • siRNA
  • Liver Cancer
  • Base Sequence
  • Polycomb-Group Proteins
Tag cloud generated 12 December, 2014 using data from PubMed, MeSH and CancerIndex

Notable (4)

Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Breast CancerHOTAIR and Breast Cancer View Publications6
Liver CancerHOTAIR and Liver Cancer View Publications5
Esophageal CancerHOTAIR and Esophageal Cancer View Publications4
Lung CancerHOTAIR and Lung Cancer View Publications4

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Related Links

Latest Publications: HOTAIR (cancer-related)

Lee NK, Lee JH, Park CH, et al.
Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma.
Biochem Biophys Res Commun. 2014; 451(2):171-8 [PubMed] Related Publications
Gastric cancer is one of the major causes of cancer death worldwide; however, the mechanism of carcinogenesis is complex and poorly understood. Long non-coding RNA HOTAIR (HOX transcript antisense RNA) recently emerged as a promoter of metastasis in various cancers including gastric cancer. Here we investigated the impact of HOTAIR on apoptosis, cell proliferation and cell cycle to dissect the carcinogenesis of gastric cancer. We examined the mechanism of invasion and metastasis and analyzed the clinical significance of HOTAIR. Downregulation of HOTAIR was confirmed by two different siRNAs. The expression of HOTAIR was significantly elevated in various gastric cancer cell lines and tissues compared to normal control. si-HOTAIR significantly reduced viability in MKN 28, MKN 74, and KATO III cells but not in AGS cells. si-HOTAIR induced apoptosis in KATO III cells. Lymphovascular invasion and lymph node metastasis were more common in the high level of HOTAIR group. si-HOTAIR significantly decreased invasiveness and migration. si-HOTAIR led to differential expression of epithelial to mesenchymal transition markers. We found that HOTAIR was involved in inhibition of apoptosis and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and progression of gastric cancer.

Related: Apoptosis Stomach Cancer Gastric Cancer

Cai B, Song XQ, Cai JP, Zhang S
HOTAIR: a cancer-related long non-coding RNA.
Neoplasma. 2014; 61(4):379-91 [PubMed] Related Publications
Long non-coding RNA was dismissed as merely transcriptional "noise" in the past decades. Numerous researches have shown that lncRNAs regulated gene expression at the epigenetic level. Moreover, lncRNAs played important roles in proliferation, apoptosis and invasiveness of tumor cells, and participated in metastatic capacity of cancers. Recent studies revealed HOX transcript antisense RNA, a lncRNA with regulatory functions of transcription, could bind PRC2 and LSD1/CoREST/REST complexes and direct to the specific gene sites, resulted in H3K27 methylation and H3K4 demethylation and ultimately gene silencing. Aberrant HOTAIR expression was associated with various sites of cancers such as breast, hepatocellular, gastric, colorectal, pancreatic et al; and affected survival and prognosis of cancer patients. In this review, we introduce an overall view of HOTAIR by describing the known molecular mechanisms and potential functions of HOTAIR and summarizing the latest progresses on the research of HOTAIR in various human cancers.

Related: Cancer Prevention and Risk Reduction

Zhang X, Zhou L, Fu G, et al.
The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer.
Carcinogenesis. 2014; 35(9):2062-7 [PubMed] Related Publications
Long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), which could induce genome-wide retargeting of polycomb-repressive complex 2, trimethylates histone H3 lysine-27 (H3K27me3) and deregulation of multiple downstream genes, is involved in development and progression of esophageal squamous cell carcinoma (ESCC). We hypothesized that the functional single nucleotide polymorphisms (SNP) in HOTAIR may affect HOTAIR expression and/or its function and, thus, ESCC risk. Therefore, we examined the association between three haplotype-tagging SNPs (htSNP) across the whole HOTAIR locus and ESCC risk as well as the functional relevance of an ESCC susceptibility SNP rs920778. Genotypes were determined in three independent case-control sets consisted of 2098 ESCC patients and 2150 controls. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was investigated in vitro and in vivo. We found that the HOTAIR rs920778 TT carriers had a 1.37-fold, 1.78-fold and 2.08-fold increased ESCC risk in Jinan, Shijiazhuang and Huaian populations, respectively, compared with the CC carriers (P = 0.003, 7.7 × 10(-4) and 5.9 × 10(-4)). During inspecting functional relevance of the rs920778 SNP, we identified a novel intronic HOTAIR enhancer locating between +1719bp and +2353bp from the transcriptional start site through reporter assays. Moreover, there is an allelic regulation of rs920778 on HOTAIR expression via this enhancer in both ESCC cell lines and normal esophageal tissue specimens, with higher HOTAIR expression among T allele carriers. These results demonstrate that functional genetic variants influencing lncRNA regulation may explain a fraction of ESCC genetic basis.

Related: Cancer of the Esophagus Esophageal Cancer

Qiu JJ, Lin YY, Ye LC, et al.
Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer.
Gynecol Oncol. 2014; 134(1):121-8 [PubMed] Related Publications
OBJECTIVES: Although long non-coding RNAs (lncRNAs) are emerging as new regulators in the cancer paradigm, the involvement of lncRNAs in epithelial ovarian cancer (EOC) is just beginning to be studied. In this study, we focused on lncRNA HOX transcript antisense RNA (HOTAIR) and investigated its expression pattern, clinical significance, and biological function in EOC.
METHODS: HOTAIR expression in EOC tissues was examined and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of in vitro and in vivo assays were performed to understand the role of HOTAIR in EOC metastasis.
RESULTS: HOTAIR expression was elevated in EOC tissues, and HOTAIR levels were highly positively correlated with the FIGO stage, the histological grade of the tumor, lymph node metastasis, and reduced overall survival (OS) and disease-free survival (DFS). A multivariate analysis showed that HOTAIR expression is an independent prognostic factor of OS and DFS in patients with EOC. Additionally, the results of in vitro assays showed that the suppression of HOTAIR expression in the three highly metastatic EOC cell lines (SKOV3.ip1, HO8910-PM, and HEY-A8) significantly reduced cell migration/invasion. The results of in vivo assays further confirmed the pro-metastatic effects of HOTAIR. Moreover, the pro-metastatic effects of HOTAIR were partially mediated by the regulation of certain matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT)-related genes.
CONCLUSIONS: Our data suggest that HOTAIR plays a vital role in EOC metastasis and could represent a novel prognostic marker and potential therapeutic target in patients with EOC.

Related: Ovarian Cancer

Chiyomaru T, Fukuhara S, Saini S, et al.
Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells.
J Biol Chem. 2014; 289(18):12550-65 [PubMed] Article available free on PMC after 02/05/2015 Related Publications
HOTAIR is a long non-coding RNA that interacts with the polycomb repressive complex and suppresses its target genes. HOTAIR has also been demonstrated to promote malignancy. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition process, and the expression of miR-141 is inversely correlated with tumorigenicity and invasiveness in several human cancers. We found that HOTAIR expression is inversely correlated to miR-141 expression in renal carcinoma cells. HOTAIR promotes malignancy, including proliferation and invasion, whereas miR-141 suppresses malignancy in human cancer cells. miR-141 binds to HOTAIR in a sequence-specific manner and suppresses HOTAIR expression and functions, including proliferation and invasion. Both HOTAIR and miR-141 were associated with the immunoprecipitated Ago2 (Argonaute2) complex, and the Ago2 complex cleaved HOTAIR in the presence of miR-141. These results demonstrate that HOTAIR is suppressed by miR-141 in an Ago2-dependent manner.

Related: Apoptosis Kidney Cancer Cancer Prevention and Risk Reduction

Bhan A, Hussain I, Ansari KI, et al.
Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo.
J Steroid Biochem Mol Biol. 2014; 141:160-70 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
Antisense transcript, long non-coding RNA HOTAIR is a key player in gene silencing and breast cancer and is transcriptionally regulated by estradiol. Here, we have investigated if HOTAIR expression is misregulated by bisphenol-A (BPA) and diethylstilbestrol (DES). Our findings demonstrate BPA and DES induce HOTAIR expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of rat. Luciferase assay showed that HOTAIR promoter estrogen-response-elements (EREs) are induced by BPA and DES. Estrogen-receptors (ERs) and ER-coregulators such as MLL-histone methylases (MLL1 and MLL3) bind to the HOTAIR promoter EREs in the presence of BPA and DES, modify chromatin (histone methylation and acetylation) and lead to gene activation. Knockdown of ERs down-regulated the BPA and DES-induced expression of HOTAIR. In summary, our results demonstrate that BPA and DES exposure alters the epigenetic programming of the HOTAIR promoters leading to its endocrine disruption in vitro and in vivo.

Related: Breast Cancer MLL gene

He X, Bao W, Li X, et al.
The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis.
Int J Mol Med. 2014; 33(2):325-32 [PubMed] Related Publications
Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is associated with a variety of human cancers, such as breast, liver and lung cancer. However, whether HOTAIR can function as a molecular marker in endometrial carcinoma (EC) remains unknown. In the present study, the expression of HOTAIR in 66 EC tissues from patients with EC and 30 normal tissues from healthy age-matched control subjects was determined using quantitative reverse transcription PCR. Furthermore, using in situ hybridization, we measured HOTAIR expression in 129 formalin-fixed paraffin-embedded (FFPE) tissue sections, which included 96 tissues that matched the frozen cases, 21 other EC tissues and 12 atypical hyperplasia tissues. Correlations between HOTAIR expression and the clinicopathological characteristics of patients were analyzed. Our results revealed that HOTAIR expression in the EC tissues was significantly upregulated compared with normal tissues (p<0.001). In addition, we observed a significant association between HOTAIR expression and the EC grade (p<0.05) and lymph node metastasis (p<0.05). Moreover, in the FFPE tissues, but not the frozen tissues, we found that a higher HOTAIR expression also correlated with the depth of myometrial invasion (p=0.019) and lymphovascular space invasion (p=0.015). More importantly, patients with a higher HOTAIR expression showed significantly poorer overall survival than those with lower HOTAIR expression (p<0.05). In conclusion, our results suggest that a high expression of HOTAIR is involved in the progression of cancer and may be a novel biomarker of poor prognosis in patients with EC.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Sørensen KP, Thomassen M, Tan Q, et al.
Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer.
Breast Cancer Res Treat. 2013; 142(3):529-36 [PubMed] Related Publications
Expression of HOX transcript antisense intergenic RNA (HOTAIR)--a long non-coding RNA--has been examined in a variety of human cancers, and overexpression of HOTAIR is correlated with poor survival among breast, colon, and liver cancer patients. In this retrospective study, we examine HOTAIR expression in 164 primary breast tumors, from patients who do not receive adjuvant treatment, in a design that is paired with respect to the traditional prognostic markers. We show that HOTAIR expression differs between patients with or without a metastatic endpoint, respectively. Survival analysis shows that high HOTAIR expression in primary tumors is significantly associated with worse prognosis independent of prognostic markers (P = 0.012, hazard ratio (HR) 1.747). This association is even stronger when looking only at estrogen receptor (ER)-positive tumor samples (P = 0.0086, HR 1.985). In ER-negative tumor samples, we are not able to detect a prognostic value of HOTAIR expression, probably due to the limited sample size. These results are successfully validated in an independent dataset with similar associations (P = 0.018, HR 1.825). In conclusion, our findings suggest that HOTAIR expression may serve as an independent biomarker for the prediction of the risk of metastasis in ER-positive breast cancer patients.

Related: Breast Cancer

Zhang JX, Han L, Bao ZS, et al.
HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma.
Neuro Oncol. 2013; 15(12):1595-603 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
BACKGROUND: Long noncoding RNA Hox transcript antisense intergenic RNA (HOTAIR) has been characterized as a negative prognostic factor in breast and colon cancer patients. The clinical significance and function of HOTAIR in glioma remains unclear.
METHODS: We analyzed the clinical significance of HOTAIR in 3 different glioma cohorts with gene expression data, including correlation with tumor grade, prognosis, and molecular subtype. The function of HOTAIR in glioma was explored by performing gene set enrichment analysis and in vitro and in vivo experiments.
RESULTS: HOTAIR expression was closely associated with glioma grade and poor prognosis. Multivariate Cox regression analysis revealed that HOTAIR was an independent prognostic factor in glioblastoma multiforme patients. HOTAIR expression correlated with glioma molecular subtype, including those of The Cancer Genome Atlas. HOTAIR was preferentially expressed in the classical and mesenchymal subtypes compared with the neural and proneural subtypes. A gene set enrichment analysis designed to show gene set differences between patients with high and low HOTAIR expression indicated that HOTAIR expression was associated with gene sets involved in cell cycle progression. HOTAIR reduction induced colony formation suppression, cell cycle G0/G1 arrest, and orthotopic tumor growth inhibition.
CONCLUSION: Our data establish that HOTAIR is an important long noncoding RNA that primarily serves as a prognostic factor for glioma patient survival, as well as a biomarker for identifying glioma molecular subtypes, a critical regulator of cell cycle progression.

He Y, Meng XM, Huang C, et al.
Long noncoding RNAs: Novel insights into hepatocelluar carcinoma.
Cancer Lett. 2014; 344(1):20-7 [PubMed] Related Publications
Recent advances in non-protein coding part of human genome analysis have discovered extensive transcription of large RNA transcripts that lack of coding protein function, termed long noncoding RNAs (lncRNAs). It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in diverse diseases are not yet fully understood. Thus, it is anticipated that more efforts should be made to clarify the lncRNAs world. Moreover, accumulating studies have demonstrated that a class of lncRNAs are dysregulated in hepatocellular carcinoma(HCC) and closely related with tumorigenesis, metastasis, prognosis or diagnosis. In this review, we will briefly discuss the regulation and functional role of lncRNAs in HCC, therefore evaluating the potential of lncRNAs as prospective novel therapeutic targets in HCC.

Related: Liver Cancer

Zhang J, Zhang P, Wang L, et al.
Long non-coding RNA HOTAIR in carcinogenesis and metastasis.
Acta Biochim Biophys Sin (Shanghai). 2014; 46(1):1-5 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
Long non-coding RNAs (lncRNAs) have gained massive attention in recent years as a potentially new and crucial layer of gene regulation. LncRNAs are prevalently transcribed in the genome, but their roles in gene regulation and disease development are largely unknown. HOX antisense intergenic RNA (HOTAIR), a lncRNA located in the HOXC locus, has been shown to repress HOXD gene expression and promote breast cancer metastasis. Mechanistically, HOTAIR interacts with and recruits polycomb repressive complex 2 (PRC2) and regulates chromosome occupancy by EZH2 (a subunit of PRC2), which leads to histone H3 lysine 27 trimethylation of the HOXD locus. Moreover, HOTAIR is pervasively overexpressed in most human cancers compared with noncancerous adjacent tissues. This review summarizes the studies on the HOTAIR lncRNA over the past 6 years.

Related: Breast Cancer Non-Small Cell Lung Cancer Liver Cancer Cancer of the Pancreas Pancreatic Cancer

Liu Z, Sun M, Lu K, et al.
The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression.
PLoS One. 2013; 8(10):e77293 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
HOTAIR, a long intervening non-coding RNA (lincRNA), associates with the Polycomb Repressive Complex 2 (PRC2) and is reported to reprogram chromatin organization and promote tumor progression. However, little is known about the roles of this gene in the development of chemoresistance phenotype of lung adenocarcinoma (LAD). Thus, we investigated the involvement of HOTAIR in the resistance of LAD cells to cisplatin. In this study, we show that HOTAIR expression was significantly upregulated in cisplatin-resistant A549/DDP cells compared with in parental A549 cells. Knockdown of HOTAIR by RNA interference could resensitize the responses of A549/DDP cells to cisplatin both in vitro and in vivo. In contrast, overexpression of HOTAIR could decrease the sensitivity of A549 and SPC-A1 cells to cisplatin. We also found that the siRNA/HOTAIR1-mediated chemosensivity enhancement was associated with inhibition of cell proliferation, induction of G0/G1 cell-cycle arrest and apoptosis enhancement through regulation of p21(WAF1/CIP1) (p21) expression. Also, pcDNA/p21or siRNA/p21 could mimic the effects of siRNA/HOTAIR1 or pcDNA/HOTAIR on the sensitivity of LAD cells to cisplatin. Importantly, siRNA/p21 or pcDNA/p21 could partially rescue the effects of siRNA/HOTAIR1 or pcDNA/HOTAIR on both p21 expression and cisplatin sensitivity in LAD cells. Further, HOTAIR was observed to be significantly downregulated in cisplatin-responding LAD tissues, and its expression was inversely correlated with p21 mRNA expression. Taken together, our findings suggest that upregulation of HOTAIR contributes to the cisplatin resistance of LAD cells, at least in part, through the regulation of p21 expression.

Related: Cisplatin CDKN1A Lung Cancer

Chen FJ, Sun M, Li SQ, et al.
Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis.
Mol Carcinog. 2013; 52(11):908-15 [PubMed] Related Publications
Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern of the lncRNA HOTAIR and assess its biological role in the development and progression of esophageal squamous cell carcinoma (ESCC), HOTAIR expression in ESCC tissues and adjacent noncancerous tissues were collected from 78 patients and measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). HOTAIR correlation with clinicopathological features and prognosis was also analyzed. Suppression of HOTAIR using siRNA treatment was performed in order to explore its role in tumor progression. Notably elevated HOTAIR expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (96%, P < 0.01), showing a high correlation with cancer metastasis (P < 0.01), elevated TNM (2009) stage classification (P < 0.01), and lowered overall survival rates (P = 0.003). Multivariate analysis revealed that HOTAIR expression (P = 0.003) is also an independent prognostic factor for comparison of TNM stage (P = 0.024) and lymph node metastasis (P = 0.010). Furthermore, in vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. Thus, HOTAIR is a novel molecule involved in both ESCC progression and prognosis. Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers.

Related: Apoptosis Cancer of the Esophagus Esophageal Cancer

Endo H, Shiroki T, Nakagawa T, et al.
Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer.
PLoS One. 2013; 8(10):e77070 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
The long non-coding RNA HOTAIR has been reported to be a poor prognostic biomarker in a variety of malignant tumors. However, little is known about the association of HOTAIR with gastric cancer. We examined the expression of HOTAIR in 68 gastric cancer samples using quantitative real-time RT-PCR and analyzed its correlation with the clinical parameters. The functional role of HOTAIR was examined by generating human gastric cancer cell lines with increased or suppressed HOTAIR expression. The anchorage -independent growth was assessed by soft agar assay. The increased or suppressed HOTAIR expressing gastric cancer cells were injected into the tail vein or peritoneal cavity of immunodeficient mice to examine the effect of this molecule on metastasis and peritoneal dissemination. The expression of HOTAIR was significantly higher in cancer lesions than in adjacent non-cancerous tissues in human gastric cancers. In the diffuse type of gastric cancer, the High-HOTAIR group (HOTAIR/GAPDH > 1) showed significantly more venous invasion, frequent lymph node metastases and a lower overall survival rate compared to the Low-HOTAIR group (HOTAIR/GAPDH < 1). Colony formation on the soft agar was enhanced in a HOTAIR-dependent manner. HOTAIR-expressing MKN74 formed more liver metastasis compared to control when they were injected into the tail vein of mice. In addition, reduced expression of HOTAIR in KATO III suppressed peritoneal dissemination. These results suggest that HOTAIR plays a pivotal role in the development of gastric cancer.

Related: Stomach Cancer Gastric Cancer

Ge XS, Ma HJ, Zheng XH, et al.
HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway.
Cancer Sci. 2013; 104(12):1675-82 [PubMed] Related Publications
Long non-coding RNAs (LncRNAs) have been recently found to be pervasively transcribed in the genome and critical regulators of the epigenome. HOTAIR, as a well-known LncRNA, has been found to play important roles in several tumors. Herein, the clinical application value and biological functions of HOTAIR were focused and explored in esophageal squamous cell carcinoma (ESCC). It was found that there was a great upregulation of HOTAIR in 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. Then some specific molecules with great significance were investigated after HOTAIR overexpression using microarray and quantitative real time-polymerase chain reaction (qPCR). WIF-1 playing an important role in Wnt/β-catenin signaling pathway was selected and further tested by immunehistochemistry. Generally, inverse correlation between HOTAIR and WIF-1 expression was demonstrated both in ESCC cells and tissues. Mechanistically, HOTAIR directly decreased WIF-1 expression by promoting its histone H3K27 methylation in the promoter region and then activated the Wnt/β-catenin signaling pathway. This newly identified HOTAIR/WIF-1 axis clarified the molecular mechanism of ESCC cell metastasis and represented a novel therapeutic target in patients with ESCC.

Related: Cancer of the Esophagus Esophageal Cancer CTNNB1 gene WIF1 gene

Liu XH, Liu ZL, Sun M, et al.
The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer.
BMC Cancer. 2013; 13:464 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
BACKGROUND: The identification of cancer-associated long non-coding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. HOTAIR (HOX transcript antisense intergenic RNA) has been implicated in several cancers; however, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of HOTAIR in NSCLC and to evaluate its biological role and clinical significance in tumor progression.
METHODS: Expression of HOTAIR was analyzed in 42 NSCLC tissues and four NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of HOTAIR. The effect of HOTAIR on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Tail vein injection of cells was used to study metastasis in nude mice. Protein levels of HOTAIR targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed).
RESULTS: HOTAIR was highly expressed both in NSCLC samples and cell lines compared with corresponding normal counterparts. HOTAIR upregulation was correlated with NSCLC advanced pathological stage and lymph-node metastasis. Moreover, patients with high levels of HOTAIR expression had a relatively poor prognosis. Inhibition of HOTAIR by RNAi decreased the migration and invasion of NSCLC cells in vitro and impeded cell metastasis in vivo. HOXA5 levels were affected by HOTAIR knockdown or over-expression in vitro.
CONCLUSIONS: Our findings indicate that HOTAIR is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion and metastasis, partially via the down-regulation of HOXA5. Thus, HOTAIR may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.

Related: Apoptosis Non-Small Cell Lung Cancer Lung Cancer MMP2 MMP9: matrix metallopeptidase 9

Li X, Wu Z, Mei Q, et al.
Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis and exhibits oncogenic activity in oesophageal squamous cell carcinoma.
Br J Cancer. 2013; 109(8):2266-78 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
BACKGROUND: HOX transcript antisense RNA (HOTAIR), which is expressed from the homebox C gene (HOXC) locus, is capable of reprogramming chromatin organisation and promoting cancer cell metastasis and can simultaneously bind the polycomb repressive complex 2, which enhances H3K27 trimethylation, and the LSD1-CoREST-REST complex, which is critical for H3K4 demethylation. Clinically, the overexpression of HOTAIR is a powerful predictor of the tumour progression and overall survival in patients with diverse cancers. The relationship between HOTAIR and oesophageal squamous cell carcinoma (ESCC), however, remains unclear. We investigated the role of HOTAIR in the pathogenesis of ESCC.
METHODS: We used quantitative real-time PCR to determine the level of HOTAIR in ESCC cell lines and 100 ESCC samples from patients; 56 adjacent non-neoplastic tissues were used as controls. We measured the effect of HOTAIR knockdown and overexpression in ESCC cell lines using colony formation assays, anchorage-independent growth assays, the CCK-8 assay, transwell migration and invasion assays, and Annexin V-binding assays. We analysed the growth of ESCC xenograft tumours in nude mice. Changes in the gene expression and methylation levels in ESCC cell lines were analysed using gene expression microarrays and the Infinium HumanMethylation450K BeadChip assay, respectively. results: The levels of HOTAIR were increased in ESCC cell lines and patient samples compared with the controls; the expression levels correlated with the disease stage and survival time. The knockdown of HOTAIR in the KYSE510 and KYSE180 ESCC cell lines using small hairpin RNAs (shRNAs) reduced the ability of the cells to form foci, migrate, and invade the extracellular matrix in culture, altered cell cycle progression, and increased the sensitivity of the cells to apoptosis. The HOTAIR knockdown reduced cancer cell metastasis in vivo, and the tumours formed by HOTAIR-silenced ESCC cells were smaller, both in size and weight, than the tumours and metastases formed by the shRNA vector control cells in a mouse xenograft model. The results of the gene microarray study showed that HOTAIR reprogrammed the gene expression profile of ESCC cells, and the gene ontology analysis revealed an enrichment in genes that are important for tumorigenesis, such as genes involved in cell migration and the regulation of the cell cycle. Comparing the gene expression profiles and DNA methylation analysis between the KYSE180 and KYSE180_HOTAIR cells revealed that only a small proportion of the methylation changes were correlated with gene expression changes.
CONCLUSION: HOX transcript antisense RNA is upregulated in ESCC cell lines and patient samples, and promotes ESCC cell proliferation and tumour metastasis in mice. The knockdown of HOTAIR resulted in significant changes in gene expression, and data analysis suggested that HOTAIR-mediated gene regulation has a critical role in ESCC progression and is a novel epigenetic molecular target for treating ESCC patients.

Related: Cancer of the Esophagus Esophageal Cancer

Chiyomaru T, Yamamura S, Fukuhara S, et al.
Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR.
PLoS One. 2013; 8(8):e70372 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
OBJECTIVE: Genistein is a soy isoflavone that has antitumor activity both in vitro and in vivo. It has been shown that genistein inhibits many type of cancers including prostate cancer (PCa) by regulating several cell signaling pathways and microRNAs (miRNAs). Recent studies suggest that the long non-coding RNAs (lncRNAs) are also involved in many cellular processes. At present there are no reports about the relationship between gensitein, miRNAs and lncRNAs. In this study, we focused on miRNAs, lncRNA that are regulated by genistein and investigated their functional role in PCa.
METHOD: Microarray (SurePrint G3 Human GE 8×60K) was used for expression profiling of genistein treated and control PCa cells (PC3 and DU145). Functional assay (cell proliferation, migration, invasion, apoptosis and cell cycle assays) were performed with the PCa cell lines, PC3 and DU145. Both in vitro and in vivo (nude mouse) models were used for growth assays. Luciferase reporter assays were used for binding of miR-34a to HOTAIR.
RESULTS: 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. Knockdown (siRNA) of HOTAIR decreased PCa cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. miR-34a was also up-regulated by genistein and may directly target HOTAIR in both PC3 and DU145 PCa cells.
CONCLUSIONS: Our results indicated that genistein inhibited PCa cell growth through down-regulation of oncogenic HOTAIR that is also targeted by tumor suppressor miR-34a. These findings enhance understanding of how genistein regulates lncRNA HOTAIR and miR-34a in PCa.

Related: Apoptosis Prostate Cancer

Hajjari M, Behmanesh M, Sadeghizadeh M, Zeinoddini M
Up-regulation of HOTAIR long non-coding RNA in human gastric adenocarcinoma tissues.
Med Oncol. 2013; 30(3):670 [PubMed] Related Publications
HOTAIR is a known long non-coding RNA which has recently been associated with the progression of some cancer types. It has been reported that HOTAIR expression is correlated with SUZ12 expression level and therefore may affect the epigenetic state of cancer tissues. Here, we found aberrant up-regulation of HOTAIR in gastric adenocarcinoma samples compared with normal adjacent gastric epithelium tissues. Besides, we found that the aberrant expression of HOTAIR was associated with TNM staging and lymph node metastasis of gastric tumors. Here, a potential cooperative expression between HOTAIR and SUZ12 genes in gastric adenocarcinoma tissues is deduced. This result suggests a role for HOTAIR long non-coding RNA in gastric cancer progression.

Related: Stomach Cancer Gastric Cancer

Tang L, Zhang W, Su B, Yu B
Long noncoding RNA HOTAIR is associated with motility, invasion, and metastatic potential of metastatic melanoma.
Biomed Res Int. 2013; 2013:251098 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
Metastatic melanoma, the primary cause of skin cancer-related death, warrants new therapeutic approaches that target the regulatory machinery at molecular level. While long noncoding RNAs (lncRNAs) are dysregulated in a number of cancer types, limited data are available on the expression and function of lncRNAs in melanoma metastasis. The primary objective of this study was to investigate the role of 6 metastasis-related lncRNAs in pairs of primary melanoma and matched lymph node metastatic tissues. Among the tested lncRNAs, HOTAIR was the most highly expressed in lymph node metastasis. The role of HOTAIR in melanoma cell motility and invasion was further evaluated by knocking down HOTAIR with siRNAs. Knockdown of HOTAIR resulted in the reduction of motility and invasion of human melanoma cell line A375, as assessed by wound healing assay and Matrigel-based invasion assay. siHOTAIR also suppressed the degradation of gelatin matrix, suggesting that HOTAIR promotes gelatinase activity. Together, our study shows that HOTAIR is overexpressed in metastatic tissue, which is associated with the ability of HOTAIR to promote melanoma cell motility and invasion. These data indicate that lncRNAs may be involved in the metastasis of melanoma and provide support for further evaluation of lncRNAs in melanoma.

Related: Melanoma

Xu ZY, Yu QM, Du YA, et al.
Knockdown of long non-coding RNA HOTAIR suppresses tumor invasion and reverses epithelial-mesenchymal transition in gastric cancer.
Int J Biol Sci. 2013; 9(6):587-97 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
BACKGROUND: Over-expression of long non-coding RNA HOTAIR has been reported in several types of cancer. Yet its involvement in gastric cancer (GC) has not been well understood. The aim of present study was to examine the expression pattern of HOTAIR in GC patients, then, explore its role in promoting cancer invasion and underlying molecular mechanism.
METHODS: The expression level of HOTAIR in the tumor specimens of GC patients was quantified by Realtime RT-PCR. The correlation between HOTAIR level and clinicopathological factors as well as prognosis was then examined. Down-regulation of HOTAIR by RNA interference was applied to investigate its roles in tumor invasiveness via the view of Epithelial-to-mesenchymal transition (EMT).
RESULTS: The expression level of HOTAIR in cancer tissues was higher than that in adjacent noncancerous tissues. Expression level of HOTAIR was significantly correlated with lymph node metastasis and TNM stage. Furthermore, high expression level of HOTAIR was a predictor of poor over-all survival in GC patients. In vitro, inhibition of HOTAIR in GC cells could reduce invasiveness, as well as the expression of MMP1 and MMP3. In addition, suppression of HOTAIR could reverse EMT process.
CONCLUSIONS: HOTAIR could act as a potential predictor for over-all survival in patients with GC. Inhibition of HOTAIR could reduce invasiveness and reverse EMT process in GC cells, indicating the potential role of HOTAIR in GC diagnostics and therapeutics.

Related: Stomach Cancer Gastric Cancer

Shi X, Sun M, Liu H, et al.
Long non-coding RNAs: a new frontier in the study of human diseases.
Cancer Lett. 2013; 339(2):159-66 [PubMed] Related Publications
With the development of whole genome and transcriptome sequencing technologies, long noncoding RNAs (lncRNAs) have received increased attention. Multiple studies indicate that lncRNAs act not only as the intermediary between DNA and protein but also as important protagonists of cellular functions. LncRNAs can regulate gene expression in many ways, including chromosome remodeling, transcription and post-transcriptional processing. Moreover, the dysregulation of lncRNAs has increasingly been linked to many human diseases, especially in cancers. Here, we reviewed the rapidly advancing field of lncRNAs and described the relationship between the dysregulation of lncRNAs and human diseases, highlighting the specific roles of lncRNAs in human diseases.

Related: Cancer Prevention and Risk Reduction

Li CH, Chen Y
Targeting long non-coding RNAs in cancers: progress and prospects.
Int J Biochem Cell Biol. 2013; 45(8):1895-910 [PubMed] Related Publications
Pervasive transcription occurs in the human genome to generate thousands of RNA transcripts, and accumulating evidence suggested that the RNA molecules, without protein coding ability, have important roles in diverse biological functions. Long non-coding RNA (lncRNA), with size larger than 200 nt, is a new class of the non-coding RNA that contributes to cancer development and progression. Roles for several lncRNAs in cancers have been characterized and strategies targeting them have inhibitory effects to malignant cells in vitro and in vivo. These findings point to the potential of lncRNAs as prospective novel therapeutic targets in cancers. Recent advance in biological drugs, led by nucleic acid drugs (i.e. siRNAs, antisense oligonucleotides), suggest directions for the development of cancer therapies targeting lncRNAs. Here, we discuss the characteristics of lncRNAs regarding their synthesis, stability and functional role in cells, and emphasize their unique properties that determine their molecular functions. We then discuss the association of lncRNAs with cancers, and illustrate the anticancer effects induced upon modulating the level and function of lncRNAs. We also revisit established methods for targeting RNA molecules and discuss new agents and strategies to attenuate lncRNAs in cancer.

Related: Cancer Prevention and Risk Reduction

Nakagawa T, Endo H, Yokoyama M, et al.
Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer.
Biochem Biophys Res Commun. 2013; 436(2):319-24 [PubMed] Related Publications
HOTAIR is one of long non-coding RNAs and its expression correlates with the prognosis and metastasis in various cancers. We showed that HOTAIR expression has an important role in the development of non-small cell lung cancer (NSCLC). In this study, we examined the expression of HOTAIR in 77 NSCLCs, their corresponding normal lung tissues and 6 brain metastases by quantitative real-time RT-PCR. High expression of HOTAIR (tumor/normal ratio ⩾2) was detected in 17 patients (22.1%) and was frequently found in patients with advanced stage, lymph node metastasis or lymph-vascular invasion and short disease free interval. Furthermore, brain metastases show significantly higher HOTAIR expression compared to primary cancer tissues. HOTAIR-expressing A549 cells showed induced cell migration and anchorage-independent cell growth in vitro. These results indicate the expression of HOTAIR enhanced the aggressive behavior of NSCLC cells.

Related: Non-Small Cell Lung Cancer Lung Cancer

Lv XB, Lian GY, Wang HR, et al.
Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival.
PLoS One. 2013; 8(5):e63516 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
BACKGROUND: It is currently unclear whether the expression of HOX transcript antisense RNA (HOTAIR) correlates with the progression of esophageal cancer. The aim of this study was to examine HOTAIR expression in patients with esophageal squamous cell cancer (ESCC) and explore its clinical significance.
METHODS: Differences in the expression of HOTAIR were examined via in situ hybridization (ISH) and quantitative reverse transcriptase PCR (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Proliferation, colony formation and migration assays were performed in ESCC cell lines to determine the function of HOTAIR in the progression of ESCC in vitro.
RESULTS: A notably higher level of HOTAIR expression was found in ESCC tissues. High expression levels of HOTAIR in ESCC patients correlated positively with clinical stage, TNM classification, histological differentiation and vital status. HOTAIR expression was found to be an independent prognostic factor in ESCC patients. ESCC patients who expressed high levels of HOTAIR had substantially lower overall 5-year survival rates than HOTAIR-negative patients. In vitro assays of ESCC cell lines demonstrated that HOTAIR mediated the proliferation, colony formation and migratory capacity of ESCC cells.
CONCLUSION: HOTAIR is a potential biomarker for ESCC prognosis, and the dysregulation of HOTAIR may play an important role in ESCC progression.

Related: Cancer of the Esophagus Esophageal Cancer

Nakayama I, Shibazaki M, Yashima-Abo A, et al.
Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells.
Int J Oncol. 2013; 43(1):63-71 [PubMed] Related Publications
Small and large non-coding RNAs (ncRNAs) contribute to the acquisition of aggressive tumor behavior in diverse human malignancies. Two types of ncRNAs, miRNA‑10b (miR-10b) and homemobox (HOX) transcript antisense RNA (HOTAIR), can suppress the translation of the HOXD10 gene, an mRNA encoding a transcriptional repressor that inhibits the expression of cell migration/invasion-associated genes. Using epithelial ovarian cancer cell lines and primary tumors, we investigated whether miR‑10b and/or HOTAIR can regulate the expression of HOXD10, and whether it permits gain of pro‑metastatic gene products, matrix metallopeptidase 14 (MMP14) and ras homolog family member C (RHOC). Overexpression of miR-10b induced a decrease in HOXD10 protein expression, and upregulated the migration and invasion abilities in ovarian cancer cell lines (P<0.05). In these cells, a significant increase of MMP14 and RHOC protein was observed. No significant upregulation of the HOXD10 protein was observed in cells with the treatment of HOTAIR-siRNA. Positive signals for HOXD10 and MMP14 proteins were observed in 47 (69%) and 25 (37%) of 68 patients with epithelial ovarian cancers. An inverse correlation between HOXD10 and MMP14 immunoreactivities was observed (P<0.05), and miR-10b expression was also inversely correlated with HOXD10 protein expression (P<0.05). These results suggested that downregulation of HOXD10 expression by miR-10b overexpression may induce an increase of pro-metastatic gene products, such as MMP14 and RHOC, and contribute to the acquisition of metastatic phenotypes in epithelial ovarian cancer cells.

Related: Ovarian Cancer RHOC

Zhuang Y, Wang X, Nguyen HT, et al.
Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen.
J Hematol Oncol. 2013; 6:35 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
BACKGROUND: The tumor microenvironment is a crucial determinant in tumor progression. Interstitial extracellular matrix (ECM), such as type I collagen (Col-1), is aberrantly enriched in the tumor microenvironment and promotes tumor progression. Long intergenic non-coding RNAs (lincRNA) are a new family of regulatory RNAs that modulate fundamental cellular processes via diverse mechanisms.
FINDINGS: We investigated whether the expression of lincRNAs was regulated by the tumor promoting Col-1. In a three-dimensional organotypic culture model using the reconstituted basement membrane ECM Matrigel (rBM 3-D), supplementation of Col-1 disrupted acini, a differentiation feature of well-differentiated lung adenocarcinoma cells, and concurrently induced the expression of a tumor-promoting lincRNA, HOX transcript antisense RNA (HOTAIR). Induction of HOTAIR by Col-1 was diminished by a neutralizing antibody against the Col-1 receptor α2β1 integrin. Col-1 activates the expression of a reporter gene controlled by the human HOTAIR promoter. Moreover the expression of HOTAIR and Col-1 was concurrently up-regulated in human non-small cell lung cancer.
CONCLUSIONS: Our findings indicate that tumor-promoting Col-1 up-regulates the expression of HOTAIR in NSCLC cells. These initial results warrant further investigation of HOTAIR and other lincRNA genes in lung tumorigenesis.

Related: Non-Small Cell Lung Cancer Lung Cancer

Bhan A, Hussain I, Ansari KI, et al.
Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol.
J Mol Biol. 2013; 425(19):3707-22 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
HOTAIR (HOX antisense intergenic RNA) is a long noncoding RNA (lncRNA) that is transcribed from the antisense strand of homeobox C gene locus in chromosome 12. HOTAIR coordinates with chromatin-modifying enzymes and regulates gene silencing. It is overexpressed in various carcinomas including breast cancer. Herein, we demonstrated that HOTAIR is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells. We also demonstrated that HOTAIR is transcriptionally induced by estradiol (E2). Its promoter contains multiple functional estrogen response elements (EREs). Estrogen receptors (ERs) along with various ER coregulators such as histone methylases MLL1 (mixed lineage leukemia 1) and MLL3 and CREB-binding protein/p300 bind to the promoter of HOTAIR in an E2-dependent manner. Level of histone H3 lysine-4 trimethylation, histone acetylation, and RNA polymerase II recruitment is enriched at the HOTAIR promoter in the presence of E2. Knockdown of ERs and MLLs downregulated the E2-induced HOTAIR expression. Thus, 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.

Related: Apoptosis Breast Cancer MLL gene MLL3 gene

Ishibashi M, Kogo R, Shibata K, et al.
Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma.
Oncol Rep. 2013; 29(3):946-50 [PubMed] Related Publications
The functions of many long non-coding RNAs (ncRNAs) in human cancers have not yet been elucidated. The long ncRNA HOTAIR is expressed from the developmental HOXC locus located on chromosome 12q13.13. Previous reports have demonstrated that HOTAIR associates with chromatin modifications in cooperation with the Polycomb complex PRC2, and promotes breast and colorectal cancer metastasis. In this study, we examined the clinical significance of HOTAIR expression in patients with hepatocellular carcinoma (HCC). HOTAIR expression was detected in primary HCCs in 13 out of 64 patients. Patients with HOTAIR expression had significantly poorer prognoses and a larger primary tumor size than those without HOTAIR expression, similar to studies in breast and colorectal cancers. Moreover, introduction of human HOTAIR into liver cancer cells revealed that HOTAIR promoted more rapid proliferation compared to control cells. Thus, although the clinical significance of HOTAIR expression in HCC may not be as pronounced as that in breast and colorectal cancers, the current study demonstrates that HOTAIR expression is associated with HCC progression, warranting further studies.

Related: Liver Cancer

Nie Y, Liu X, Qu S, et al.
Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival.
Cancer Sci. 2013; 104(4):458-64 [PubMed] Related Publications
Identification of new nasopharyngeal carcinoma (NPC) biomarkers is of great clinical value for the diagnosis and treatment of NPC. HOTAIR, a cancer-related long non-coding RNA, was tested and its prognostic value for NPC was evaluated. As determined using in situ hybridization (ISH), 91 of 160 (56.87%) paraffin-embedded NPC biopsies showed high expression levels of HOTAIR (staining index score ≥ 6). HOTAIR was upregulated in tumors with a large size (P = 0.021), more advanced clinical stage (P = 0.012) and increased lymph node tumor burden (P = 0.005). Quantified using real-time PCR, HOTAIR expression levels in fresh tissue and paraffin-embedded samples were 5.2 ~ 48.4-fold higher compared with non-cancer tissue samples. Moreover, HOTAIR expression levels increased with clinical stage progression, which was consistent with ISH findings in the paraffin-embedded tissue. Most importantly, NPC patients with higher HOTAIR levels had a poor prognosis for overall survival using univariate and multivariate analysis. In addition, HOTAIR mediated the migration, invasion and proliferation of NPC cells in vitro. HOTAIR is a potential biomarker for the prognosis of NPC, and dysregulation of HOTAIR might play an important role in NPC progression.

Related: Nasopharyngeal Cancer


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Cite this page: Cotterill SJ. HOTAIR, Cancer Genetics Web: http://www.cancerindex.org/geneweb/HOTAIR.htm Accessed: date

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