Expression Level Of HOX Transcript Antisense RNA Research Articles

Long non-coding RNA HOTAIR promotes cancer cell energy metabolism in pancreatic adenocarcinoma by upregulating hexokinase-2.

Hox transcript antisense RNA (HOTAIR) is a long non-coding RNA (lncRNA) that serves a key role in the pathogenesis of various types of cancer, including pancreatic adenocarcinoma. However, the diagnostic and prognostic values of HOTAIR in pancreatic adenocarcinoma, as well as its involvement in cancer cell energy metabolism, remain unclear. In the present study, tumor tissues and adjacent healthy tissues were collected from patients with pancreatic adenocarcinoma, and blood samples were collected from patients and healthy controls. Expression levels of HOTAIR and hexokinase-2 (HK2) were detected by reverse transcription-quantitative polymerase chain reaction. All patients were followed up for 5 years, and the diagnostic and prognostic values of serum HOTAIR levels were investigated by receiver operating characteristic curve and survival analyses, respectively. Pancreatic adenocarcinoma cell lines overexpressing HOTAIR and HK2 were established, and the effects on cell proliferation, lactate production, glucose uptake and ATP production were detected by Cell Counting Kit-8, lactate, glucose uptake and ATP assays, respectively. The protein expression was detected by western blot analysis. The results revealed that HOTAIR and HK2 expression levels were increased in tumor tissues compared with adjacent healthy tissues. The serum levels of HOTAIR and HK2 were higher in patients with pancreatic cancer compared with healthy controls. The serum levels of these two factors may be used to accurately predict pancreatic adenocarcinoma and its prognosis. HOTAIR and HK2 overexpression led to the promotion of tumor cell proliferation. HOTAIR overexpression increased lactate production, glucose uptake and ATP production. Furthermore, it promoted HK2 expression, however HK2 overexpression displayed no significant effects on HOTAIR expression levels. Therefore, it was concluded that the lncRNA HOTAIR may promote cancer cell energy metabolism in pancreatic adenocarcinoma by upregulating HK2.

Long non-coding RNA HOTAIR regulates the development of non-small cell lung cancer through miR-217/DACH1 signaling pathway.

Long non-coding RNA HOX transcript antisense RNA (HOTAIR) is reported to make chromatin state, cell growth and cancer metastasis. However, the role of HOTAIR in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to explore the regulatory mechanism of HOTAIR in NSCLC in relation to miR-217/Dachshund homolog 1 (DACH1) signaling pathway. The expression levels of HOTAIR and miR-217 were measured by quantitative Polymerase Chain Reaction (qPCR) in NSCLC cell lines and human bronchial epithelial cell line HBE. The direct target of HOTAIR and miR-217 in NSCLC was confirmed by a Luciferase reporter assay. The expression of DACH1 protein was examined by Western blot (WB) assay. Cell migration and invasion were examined with transwell assays, and cell proliferation was measured by Cell Counting Kit-8 (CCK8) assay. HOTAIR was up-regulated and miR-217 was down-regulated in NSCLC cell lines. Silencing of HOTAIR significantly repressed cell proliferation and inhibited cell migration and invasion in H1299 and A549 cells by facilitating miR-217 expression. Moreover, bioinformatics analysis and Luciferase reporter assay confirmed that DACH1 was a target of miR-217. Furthermore, the overexpression of miR-217 markedly repressed cell proliferation and inhibited cell migration and invasion in H1299 and A549 cells. DACH1 reverses the effects of miR-217 overexpression in NSCLC cells. HOTAIR was up-regulated in NSCLC cell and regulates the proliferation, migration, invasion through the miR-217/DACH1 signaling pathway. It provides a novel potential treatment strategy for NSCLC.

HOTAIR promotes myocardial fibrosis through regulating URI1 expression via Wnt pathway.

To investigate whether HOX transcript antisense RNA (HOTAIR) regulates myocardial fibrosis via promoting proliferation of cardiac fibroblasts (CFs) and upregulating the expression levels of fibrotic proteins through activating Wnt signaling pathway. The expression level of HOTAIR in Ang II-induced cardiac fibroblasts was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). Overexpression or knockdown of HOTAIR expression was achieved by lentivirus transfection. The effects of HOTAIR on regulating cell proliferation, migration and apoptosis were measured by cell counting kit-8 (CCK-8) test, transwell assay and flow cytometry, respectively. Western blot and qRT-PCR experiments were performed to detect expressions of fibrosis-related genes and Wnt pathway-related genes. Target gene of HOTAIR was predicted by bioinformatics analysis. Rescue assays were conducted to assess whether HOTAIR could regulate cell proliferation and fibrosis by activating Wnt signaling pathway via URI1. QRT-PCR results showed that HOTAIR expression in Ang II-induced CF cells was significantly higher than that in control. HOTAIR overexpression in CF cells can promote cell proliferation and migration, inhibit apoptosis, and promote the expressions of fibrosis-related genes. Western blot results indicated that HOTAIR could upregulate URI1 expression and activate Wnt signaling pathway. In addition, rescue assay demonstrated that overexpression of URI1 reversed the inhibitory effect of HOTAIR knockdown on Wnt pathway. Highly expressed HOTAIR promoted proliferation and migration of cardiac fibroblasts. HOTAIR remarkably upregulated fibrosis-related genes in CF cells. The mechanism of HOTAIR in regulating myocardial fibrosis might be related to the activation of Wnt signaling pathway through targeting URI1 expression.

Repression of PDK1- and LncRNA HOTAIR-Mediated EZH2 Gene Expression Contributes to the Enhancement of Atractylenolide 1 and Erlotinib in the Inhibition of Human Lung Cancer Cells

Background/Aims: We previously showed that the major bioactive compound of Atractylodes macrocephula Koidz atractylenolide 1 (ATL-1) inhibited human lung cancer cell growth by suppressing the gene expression of 3-Phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1). However, the potentially associated molecules and downstream effectors of PDK1 underlying this inhibition, particularly the mechanism for enhancing the anti-tumor effects of epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs), remain unknown. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Western blot analyses were performed to examine the protein expressions of PDK1 and of zeste homolog 2 (EZH2). The levels of long non-coding RNA (lncRNA) and HOX transcript antisense RNA (HOTAIR) were examined via qRT-PCR. RNA-binding protein immunoprecipitation assays were used to analyze HOTAIR interaction with EZH2. The promoter activity of the EZH2 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expressions of PDK1, HOTAIR, and EZH2 were conducted via transient transfection assays. A xenografted tumor model was used to further evaluate the effect of ATL-1 in the presence or absence of erlotinib in vivo. Results: We showed that the combination of ATL-1 and EGFR-TKI erlotinib further inhibited growth and induced cell arrest of the human lung cancer cells, determined by both MTT and flow cytometry assays. ATL-1 inhibited the protein expression and the promoter activity of EZH2, which was reversed in cells with PDK1 overexpression. Interestingly, ATL-1 inhibited the expression levels of HOTAIR. While silencing HOTAIR inhibited the expressions of PDK1 and EZH2, overexpression of HOTAIR reduced the ATL-1-reduced PDK1 and EZH2 protein expressions and EZH2 promoter activity. In addition, ATL-1 reduced the HOTAIR binding to the EZH2 protein. Moreover, we found that exogenously expressed EZH2 antagonized the effect of ATL-1 on cell growth inhibition. Consistent with the in vitro results, ATL-1 inhibited tumor growth and the expression levels of HOTAIR, protein expressions of EZH2 and PDK1 in vivo. Importantly, there was synergy of the combination of ATL-1 and erlotinib in this process. Conclusion: Here, we provide the first evidence that ATL-1 inhibits lung cancer cell growth through inhibiting not only the PDK1 but also the lncRNA HOTAIR, which results in the reduction of one downstream effector EZH2 expression. The novel interplay between the HOTAIR and EZH2, as well as repressions of the PDK1 and HOTAIR coordinate the overall effects of ATL-1. Importantly, the combination of ATL-1 and EGFR-TKI erlotinib exhibits synergy. Thus, targeting the PDK1- and HOTAIR-mediated downstream molecule EZH2 by the combination of ATL-1 and erlotinib potentially facilitates the development of an additional novel strategy to combat lung cancer.

LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway

Background/Aims: HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). Methods: We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells. The possible mechanisms of HOTAIR were also explored by fluorescence reporter assay and Western blot. Results: The expressions of HOTAIR were upregulated in CRC tissue tissues compared to adjacent control tissues. We also found HOTAIR was downregulated by miR-203a-3p in CRC cell lines. Both HOTAIR knockdown and miR-203a-3p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and GRG5 were inhibitory targets of miR-203a-3p, and that Wnt/β-catenin signaling was inhibited by both HOTAIR knockdown and miR-203a-3p overexpression. Significantly, we found that increased expression of miR-203a-3p is essential for cell proliferation repression, chemoresistance reduction, and Wnt/β-catenin signaling inhibition induced by HOTAIR knockdown. Conclusions: Our study demonstrated that the lncRNA HOTAIR could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-203a-3p and the activity of Wnt/β-catenin signaling pathway.

High expression of long non‑coding HOTAIR correlated with hepatocarcinogenesis and metastasis.

HOX transcript antisense RNA (HOTAIR), a newly discovered long noncoding RNA (lncRNA), has been reported to be a poor prognostic marker in many types of cancers. The current study attempted to investigate the biological roles and clinicopathlogical implications of HOTAIR in hepatocellular carcinoma (HCC), as well as understand the molecular mechanisms of HOTAIR in HCC progression. HOTAIR expression in 95 HCC patients with paired HCC tissues and adjacent non‑cancer tissues were investigated using quantitative reverse transcription‑polymerase chain reaction. The association between HOTAIR expression and clinicopathological features was assessed. The effects of HOTAIR were examined invitro assays by silencing the lncRNA. Pathway analyses were performed to illustrate the biological functions of the HOTAIR and coexpression genes. The expression level of HOTAIR was observed significantly higher in the HCC tissue than the adjacent non‑tumor tissue. HOTAIR expression levels were significantly higher in tumor samples from patients with distant metastasis, advanced stage, portal vein tumor embolus, vasoinvasion, tumor capsular infiltration or positive nm23 expression than those from patients without these conditions, correspondingly. The silencing of HOTAIR in liver cancer cells induced the inhibition of cell proliferation and promotion of apoptosis. Several pathways such as extracellular matrix‑receptor interaction, focal adhesion, pathways in cancer were annotated with the HOTAIR and coexpression genes. In summary, the present analysis indicates that HOTAIR might be an oncogene in HCC. It functions though promoting tumor cell growth and inhibiting apoptosis. HOTAIR may potentially be involved in HCC metastatic progression by several pathways correlated to cell adhesion, and may be a therapeutic target in future.

Serum HOTAIR as a novel diagnostic biomarker for esophageal squamous cell carcinoma

BackgroundEarly diagnosis of esophageal squamous cell carcinoma (ESCC) is an important issue to improve the prognosis. HOX transcript antisense RNA (HOTAIR), a long noncoding RNA (lncRNA) expressed from the HOXC locus, has been recently revealed as an oncogenic regulator in ESCC. This study aimed to investigate whether serum HOTAIR is involved in the diagnosis of ESCC.MethodsIn this study, we detected serum HOTAIR expression in 50 patients with ESCC (including 42 tumor resection and 8 without surgery) and 20 healthy volunteers to investigate the role of serum HOTAIR in ESCC using the quantitative real-time polymerase chain reaction (qRT-PCR) method.ResultsClinical data indicated that serum HOTAIR were correlated with TNM stage. The expression level of serum HOTAIR (0.189 ± 0.010) was significantly higher in ESCC patients compared with that of healthy controls (0.055 ± 0.008, P < 0.01). The ROC curve analysis yielded an area under the ROC curve (AUC) value of 0.793 (95% CI: 0.692 to 0.895, P < 0.01). Also, the serum HOTAIR expression level decreased obviously in postoperative samples (one month after the surgery) compared to preoperative specimens. Moreover, there was a significant correlation between serum HOTAIR expression and the expression of HOTAIR in ESCC tissue according to Pearson correlation analysis.ConclusionsOur study, for the first time, demonstrated that serum HOTAIR might serve as a potential biomarker for the diagnosis of ESCC.

Overexpression of LncRNA HOTAIR is Associated with Poor Prognosis in Thyroid Carcinoma: A Study Based on TCGA and GEO Data.

The role of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in thyroid carcinoma (TC) remains unclear. The current study was aimed to assess the clinical value of HOTAIR expression levels in TC based on publically available data and to evaluate its potential signaling pathways. The expression data of HOTAIR and clinical information concerning TC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Furthermore, 3 online biological databases, Starbase, Cbioportal, and Multi Experiment Matrix, were used to identify HOTAIR-related genes in TC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Panther pathway analyses were then undertaken to study the most enriched signaling pathways in TC (EASE score<0.1, Bonferroni<0.05). The TCGA results demonstrated that the expression level of HOTAIR in TC tissues was significantly increased compared with non-cancerous tissues (p<0.001). HOTAIR over-expression was significantly associated with poor survival in TC patients (p=0.03). Meta-analyses of GEO datasets revealed a trend consistent with the above results on HOTAIR expression levels in TC (SMD=0.23; 95%CI, 0.00-0.45; p=0.047). Finally, the results of functional analysis for HOTAIR-related genes indicated that HOTAIR might participate in tumorigenesis via the Wnt signaling pathway. In conclusion, our study demonstrates that HOTAIR may be involved in thyroid carcinogenesis, and the over-expression of HOTAIR could act as a biomarker associated with a poor outcome in TC patients. Moreover, the Wnt signaling pathway may be the key pathway regulated by HOTAIR in TC.

Effects of irradiation on radioresistance, HOTAIR and epithelial-mesenchymal transition/cancer stem cell marker expression in esophageal squamous cell carcinoma.

Radiotherapy is a common therapeutic strategy used to treat esophageal squamous cell carcinoma (ESCC). However, tumor cells often develop radioresistance, thereby reducing treatment efficacy. Here, we aimed to identify the mechanisms through which ESCC cells develop radioresistance and identify associated biomarkers. Eca109 cells were exposed to repeated radiation at 2 Gy/fraction for a total dose of 60 Gy (Eca109R60/2Gy cells). MTT and colony formation assays were performed to measure cell proliferation and compare the radiation biology parameters of Eca109 and Eca109R60/2Gy cells. Cell cycle distributions and apoptosis were assessed by flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blotting were employed to analyze the expression of HOX transcript antisense RNA (HOTAIR), in addition to biomarkers of the epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Eca109R60/2Gy cells exhibited increased cell proliferation and clone formation, with significantly higher radiobiological parameters compared with the parental Eca109 cells. The Eca109R60/2Gy cells also exhibited significantly decreased accumulation in G2 phase and increased accumulation in S phase. Additionally, the apoptosis rate was significantly lower in Eca109R60/2Gy cells than in parental Eca109 cells. Finally, HOTAIR expression levels and SNAI1 and β-catenin mRNA and protein expression levels were significantly higher, whereas E-cadherin levels were significantly lower in Eca109R60/2Gy cells than in Eca109 cells. Therefore, our findings demonstrated that radioresistance was affected by the expression of HOTAIR and biomarkers of the EMT and CSCs.

The expression and significance of HOX transcript antisense RNA and epithelial-mesenchymal transition-related factors in esophageal squamous cell carcinoma.

The present study investigated the correlation and significance of HOX transcript antisense RNA (HOTAIR) and epithelial-mesenchymal transition (EMT)-related factors in the occurrence and metastasis of esophageal squamous cell cancer (ESCC) progression. The mRNA and protein expression levels of HOTAIR and EMT‑related factors were detected in 96 ESCC and para‑carcinoma tissues using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The expression levels of these factors, and the correlation between these factors and clinicopathological characteristics were subsequently analyzed. HOTAIR mRNA expression levels were significantly higher in ESCC compared with in para-carcinoma tissues, and HOTAIR mRNA expression levels were significantly higher in the groups with lymph node involvement or organ metastasis compared with the group without. Furthermore, HOTAIR expression levels demonstrated a significant increasing trend from well‑differentiated cancer to poorly differentiated cancer. The mRNA and protein expression levels of zinc finger protein SNAI1 (Snail) and β‑catenin in ESCC were significantly higher compared with para-carcinoma tissues, whereas E‑cadherin mRNA and protein expression levels were lower in ESCC tissues compared with in para-carcinoma tissues. Snail mRNA and protein expression levels were also significantly higher in groups with lymph node involvement or organ metastasis compared with those without, and β‑catenin protein expression levels were significantly higher in the groups with lymph node involvement or organ metastasis compared with the group without. In the 96ESCC tissues, HOTAIR mRNA expression levels were positively correlated with Snail mRNA and protein expression levels, and were negatively correlated with E‑cadherin expression levels. HOTAIR mRNA expression levels were also positively correlated with β‑catenin mRNA expression levels. In conclusion, HOTAIR may be involved in carcinogenesis and metastasis, and may induce the expression of EMT‑related factors; detection of these factors may assist in early diagnosis and prognostic prediction.

Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence.

The present study aimed to investigate the expression level of HOX transcript antisense RNA (HOTAIR) in hepatocellular carcinoma (HCC) and its association with various clinicopathological characteristics, and to further explore the molecular mechanisms of HOTAIR function in HCC. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of HOTAIR in 60 paired fresh HCC samples and adjacent normal liver tissue samples. The association between HOTAIR expression and clinicopathological parameters was analyzed. Lentivirus-mediated HOTAIR-specific small hairpin RNA vectors were transfected into HepG2 cells. Cell proliferation and invasion in vitro were examined by MTT and Transwell assays, respectively. A xenograft model was used to analyze the tumorigenesis of liver cancer cells in vivo. In addition, semi-quantitative RT-PCR was used to detect the expression level of Wnt/β-catenin signaling molecules under the condition of HOTAIR inhibition. The results revealed that the expression level of HOTAIR in HCC tissues was higher than that in adjacent non-cancerous tissues. HOTAIR expression was significantly associated with poor tumor differentiation (P=0.002), metastasis (P=0.002) and early recurrence (P=0.001). In vitro, the inhibition of HOTAIR in liver cancer cells resulted in the suppression of cell proliferation and invasion. HOTAIR depletion significantly inhibited the rate of growth of liver cancer cells in vivo. Furthermore, the expression levels of Wnt and β-catenin were downregulated when HOTAIR expression was suppressed. In conclusion, HOTAIR is important in the progression and recurrence of HCC, partly through the regulation of the Wnt/β-catenin signaling pathway. Targeting HOTAIR may be a novel therapeutic strategy for HCC.

Influence of long noncoding RNA HOTAIR on human glioma cell metabolism and growth

Objective To investigate the influence of long noncoding RNA HOX transcript antisense RNA (HOTAIR) on human glioma cell metabolism and growth. Methods The fluorescently labeled small interfering (si-HOTAIR) was used to transfect glioma U87 and U251 cell lines. The real-time polymerase chain reaction (RT-PCR) was used to detect the expression level of HOTAIR in glioma cells. CCK8 test and colony formation assay were used to detect the growth changes of the glioma cells. Seahorse BioScience XF glycilysis stress test kit and XF mitochondrial stress test kit were used to detect the cell aerobic glycolysis and mitochondrial function. Western blot was used to detect glycolysis related enzymes, including the expression levels of glucose-6-phosphate isomerase (GPI), Pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA). Results The transfection efficiency of si-HOTAIR in U87and U251cells observed under a fluorescence microscope was more than 90%. The HOTAIR expression in the cells of the si-HOTAIR group was downregulated significantly compared with the negative control group (P<0.01). The proliferative ability and clonal formation ability of the U87and U251 glioma cells of the si-HOTAIR group were significantly lower that than those of the negative group (P<0.01). After downregulation of HOTAIR, the aerobic glycolysis capacity of glioma cells were diminished, showing reduced based glycolysis level (P<0.05), diminished maximum glycolytic capacity (P<0.01), and decreased remaining amount of glycolysis (P<0.01). The expression levels of GPI, PKM2 and LDHA of the si-HOTAIR group were lower than those of the negative control group (P<0.01). After downregulation of HOTAIR, the mitochondrial function in glioma cells was impaired, showing decreased basal respiration level (U87 cells P<0.01), decreased mitochondrial coupling efficiency, and diminished residual respiration ability (P<0.05). Conclusions Downregulation of HOTAIR expression may impair the glycolytic capacity and mitochondrial function of glioma cells, simultaneously influence the growing ability of glioma cells. Key words: Glioma; Mitochondria; Metabolism; Glycolysis; Proliferation; Long noncoding RNA; HOX transcript antisense RNA

Enhancing HOTAIR/MiR-10b Drives Normal Liver Stem Cells Toward a Tendency to Malignant Transformation Through Inducing Epithelial- to-Mesenchymal Transition.

Previously, other groups and our team consistently have demonstrated that the possible origination of liver cancer stem cells (LCSCs) is the malignant transformation from liver normal stem cells (LNSCs). However, this complex and multi-step process is far from clear due to the accumulation of various gene dysregulations. Because non-coding RNAs (ncRNAs) could regulate multiple genes, a family of genes, and even whole chromosomes, this study further investigated the effect of dysregulated short ncRNA microRNA-10b and long ncRNA HOX transcript antisense RNA (HOTAIR) between LNSCs and LCSCs on phenotype reversion. To clarify the role of ncRNA in malignant transformation of LNSCs, we used lentivirus transduction to enhance the miR-10b and HOTAIR expression levels in our previously isolated rat LNSCs. The malignant abilities of proliferation, invasiveness, and tumorigenesis were observed and compared in cells before and after ncRNAs enhancement. After microRNA-10b and HOTAIR were enhanced separately, several cancer stem cell (CSC)-like traits appeared in these LNSCs, including in vitro-enhanced proliferative capacity, expression of putative LCSC markers, progressive invasive ability, and even in vivo aggravation into and taking the place of normal liver tissue. Furthermore, strengthened expression of these ncRNAs partially degraded E-cadherin in LNSCs, which is one of the classic markers in epithelial-to-mesenchymal transition (EMT). HOTAIR or miR-10b enhanced in LNSCs may drive the LNSCs to a tendency toward malignant transformation. This study partially uncovers the mechanism by which miR-10b or HOTAIR promotes malignant transformation of LNSCs through down-regulating E-cadherin and inducing EMT.

THU0115 Epigenetic Repression of the Long Noncoding Rna Hotair Regulates NF-KB Signalling and the Expression of Matrix Metalloproteases in Synovial Fibroblasts

BackgroundLong noncoding RNAs (lncRNA, >200nt) influence gene expression through their interaction with transcription factors and/or epigenetic enzymes. We have shown that the histone methyltransferase EZH2 is upregulated in rheumatoid arthritis...

Long Noncoding RNA HOTAIR Is a Prognostic Marker for Esophageal Squamous Cell Carcinoma Progression and Survival

BackgroundIt 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.MethodsDifferences 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.ResultsA 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.ConclusionHOTAIR is a potential biomarker for ESCC prognosis, and the dysregulation of HOTAIR may play an important role in ESCC progression.

Upregulation of the long non‐coding rna hotair promotes esophageal squamous cell carcinoma metastasis and poor prognosis

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.