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Objective It is essential to characterize underlying molecular mechanism associated with head and neck squamous cell carcinoma (HNSCC) and identify promising therapeutic targets. Herein, we explored role of homeobox transcript antisense RNA (HOTAIR) in HNSCC to regulate stanniocalcin‐2 (STC2) by sponging microRNA‐206 (miR‐206). Methods HNSCC‐related differentially expressed genes and regulation network amongst HOTAIR, miR‐206 and STC2 were identified. Next, effect of HOTAIR on cell biological functions of HNSCC was identified after transfection of cells with HOTAIR overexpressed plasmids or siRNA against HOTAIR. PI3K/AKT signalling pathway‐related gene expression was measured after miR‐206 and STC2 were suppressed. Cell invasion, migration and proliferation were assessed. Finally, tumour growth was assessed to determine the effects of HOTAIR/miR‐206/STC2 axis in vivo. Results HOTAIR specifically bound to miR‐206 and miR‐206 targeted STC2. Downregulated HOTAIR or upregulated miR‐206 suppressed HNSCC cell proliferation, invasion and migration. miR‐206 inhibited PI3K/AKT signalling pathway by down‐regulating STC2. Besides, silenced HOTAIR or overexpressed miR‐206 repressed the tumour growth of nude mice with HNSCC. Conclusion HOTAIR regulated HNSCC cell biological functions by binding to miR‐206 through STC2.

Homeobox transcript antisense RNA (HOTAIR), as a long intergenic non-coding RNA (lincRNA), is upregulated in various cancers and involved in diverse cellular functions. However, its role in liver fibrosis is unclear. In this study, HOTAIR expression was upregulated in hepatic stellate cells (HSCs) in vivo and in vitro during liver fibrosis. HOTAIR knockdown suppressed HSC activation including α-smooth muscle actin (α-SMA) and typeIcollagen in vitro and in vivo. Both HSC proliferation and cell cycle were inhibited by HOTAIR knockdown. Notably, inhibition of HOTAIR led to an increase in PTEN, associated with the loss of DNA methylation. miR-29b-mediated control of PTEN methylation was involved in the effects of HOTAIR knockdown. HOTAIR was confirmed a target of miR-29b and lack of the miR-29b binding site in HOTAIR prevented the suppression of miR-29b, suggesting HOTAIR contributes to PTEN expression downregulation via sponging miR-29b. Interestingly, increased HOTAIR was also observed in hepatocytes during liver fibrosis. Loss of HOTAIR additionally led to the increase in PTEN and the reduction in typeIcollagen in hepatocytes. Collectively, we demonstrate that HOTAIR downregulates miR-29b expression and attenuates its control on epigenetic regulation, leading to enhanced PTEN methylation, which contributes to the progression of liver fibrosis. Jianjian Zheng and colleagues found that HOTAIR was upregulated in activated HSCs during liver fibrosis and loss of HOTAIR suppressed HSC activation. They demonstrated that HOTAIR downregulates miR-29b and attenuates its control on DNMT3b, leading to restoration of DNMT3b and enhancement of PTEN methylation, which contributes to liver fibrosis.

Oesophageal cancer is a progressive tumour with high mortality. However, therapies aimed at treating oesophageal cancer remain relatively limited. Accumulating studies have highlighted long non‐coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), microRNA‐204 (miR‐204) and homeobox C8 (HOXC8) in the progression of oesophageal cancer. Herein, we tried to demonstrate the function of HOTAIR, miR‐204 and HOXC8 in oesophageal cancer and their relationship. Differentially expressed genes involved in oesophageal cancer were identified. The endogenous expression of HOTAIR and miR‐204 in oesophageal cancer cell lines was altered to elucidate their effects and to identify the interaction among HOTAIR, miR‐204 and HOXC8. We also explored the underlying regulatory mechanisms of HOTAIR and miR‐204 with siRNA against HOTAIR, miR‐204 mimic or miR‐204 inhibitor. Cell proliferation, migration, invasion and apoptosis were subsequently detected. Xenograft in nude mice was induced to evaluate tumourigenicity. miR‐204 was down‐regulated, while HOTAIR and HOXC8 were up‐regulated in the oesophageal cancer tissues. HOTAIR could competitively bind to miR‐204 and miR‐204 could further target HOXC8. The oesophageal cancer cells treated with si‐HOTAIR or miR‐204 mimic exhibited decreased expression levels of HOXC8, Vimentin and MMP‐9, but increased E‐cadherin level. Silenced HOTAIR or elevated miR‐204 inhibited proliferation, migration and invasion, along with stimulated apoptosis of oesophageal cancer cells. In summary, our results show that lncRNA HOTAIR could specifically bind to miR‐204 as a competing endogenous RNA and regulate miR‐204 and HOXC8. Hence, down‐regulation of HOTAIR could inhibit progression of oesophageal cancer, indicating a novel target for oesophageal cancer treatment.

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.

The current study aimed to investigate the role of long non-coding RNA (lncRNA) homeobox transcript antisense RNA (HOTAIR) in the pathogenesis of diabetic cardiomyopathy. Patients with diabetic cardiomyopathy, patients with diabetes but without cardiomyopathy and healthy controls were included in the current study. All participants underwent myocardial biopsy to collect myocardial tissues. Blood samples were also collected from each participant to prepare serum. Expression of HOTAIR in myocardial tissues was detected by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of serum HOTAIR for diabetic cardiomyopathy. AC16 human cardiomyocyte cells were treated with high glucose to observe the changes in expression of HOTAIR and phosphorylation of Akt. HOTAIR expression vector was transfected into cells of AC16 cell line and the effects of HOTAIR overexpression on cell viability and Akt phosphorylation were detected by MTT assay and western blot analysis, respectively. HOTAIR expression was significantly downregulated in myocardial tissues and serum of patients with diabetic cardiomyopathy compared with patients with diabetes and healthy controls. Serum HOTAIR could be used to effectively distinguish patients with diabetic cardiomyopathy from healthy controls. High glucose treatment inhibited HOTAIR expression and Akt phosphorylation. HOTAIR overexpression promoted Akt phosphorylation. HOTAIR overexpression improved AC16 cell viability, while PI3K/Akt inhibitor treatment reduced this effect. LncRNA HOTAIR may improve diabetic cardiomyopathy by increasing the viability of cardiomyocytes through activation of the PI3K/Akt pathway.

The aim of the present study was to investigate the radiosensitizing effects of homeobox (HOX) transcript antisense RNA (HOTAIR) long non-coding RNA on breast cancer tumor cells and examine the underlying mechanisms. Recombinant plasmid vectors containing HOTAIR gene were constructed and MDA-MB231 cells were transfected with these plasmids using liposomes. The cells were treated with radiation and cell apoptosis, proliferation, and double-stranded DNA breaks were examined. HOXD10, phosphorylated AKT (p-AKT) and p-BAD expression levels were measured using western blot analysis. The results showed a higher expression of HOTAIR in advanced tumor cells. HOTAIR efficiently enhanced radioresistance in MDA-MB231 breast cancer cells and accelerated proliferation through the Akt pathway by targeting HOXD10. In conclusion, the findings demonstrated that HOTAIR gene is a valid therapeutic target for the reversal of radiotherapy resistance in breast cancer.

Programmed cell death protein 4 (PDCD4) has recently been demonstrated to be implicated in translation and transcription, and the regulation of cell growth. However, the mechanisms underlying PDCD4 function in glioma cells remain to be elucidated. The current study investigated the function and regulation of PDCD4 and the results demonstrated that the expression of PDCD4 was significantly reduced in glioma cells compared with normal cells. When PDCD4 was overexpressed in glioma cells, the proliferation rate and invasive capability of the cells greatly decreased, suggesting that PDCD4 functions as a tumor suppressor in this cell type. In addition, the histone modification status of the PDCD4 gene was analyzed, and chromatin immunoprecipitation assay identified a high density of histone 3 lysine 27 trimethylation on the promoter of PDCD4, which was associated with the long non-coding RNA, homeobox transcript antisense RNA (HOTAIR). The expression of HOTAIR was significantly increased in glioma cells compared with normal cells, and it exerted its function in a polycomb repressive complex 2-dependent manner. These results may provide novel approaches to therapeutically target PDCD4 and HOTAIR in patients with gliomas.