HOTAIR Expression Research Articles

Long non-coding RNA HOTAIR functions as miRNA sponge to promote the epithelial to mesenchymal transition in esophageal cancer

BackgroundAccumulating evidence indicates dysregulated expression of the long non-coding RNA HOTAIR (lncRNA-HOTAIR) may play a significant role in tumor progression. LncRNA-HOTAIR promotes several processes in esophageal cancer (EC), including cell growth, differentiation, invasion and migration. However, the mechanisms by which lncRNA-HOTAIR promotes invasion and migration EC remain unclear. MethodsLncRNA-HOTAIR and miR-148a expression were quantified in 40 paired human EC and tumor-adjacent tissues and EC cell lines by quantitative real-time PCR (qRT-PCR). The CCK8 assay was used to quantify cell proliferation. Transwell invasion and migration assays were performed to assess cell invasion and migration. Western blot analysis was used to quantify E-cadherin, N-cadherin, Vimentin, and Snail2 expression. StarBase V2.0 was used to identify putative miRNA binding sites in lncRNA-HOTAIR; luciferase reporter assays were performed to validate the function of the predicted binding sites. ResultHigh lncRNA-HOTAIR expression was associated with significantly poorer overall survival in EC. In vitro analysis showed lncRNA-HOTAIR enhanced EC cell proliferation, invasion and migration, and promoted the EMT. Mechanistic investigations revealed lncRNA-HOTAIR promotes the EMT by acting as a miR-148a sponge to positively regulate Snail2 expression. ConclusionsLncRNA-HOTAIR acts as a miR-148a sponge to positively regulate Snail2 expression, enhance cell invasion and metastasis, and promote the EMT in EC. LncRNA-HOTAIR may play an important role in tumor development and progression and represent a novel therapeutic target for EC.

MicroR-545 mediates colorectal cancer cells proliferation through up-regulating epidermal growth factor receptor expression in HOTAIR long non-coding RNA dependent.

The functional impact of recently discovered miRNAs in human cancer remains to be clarified. One miRNA in colorectal cancer which has attracted attention is miR-545. In this study, we examined the function of miR-545 in proliferation of colorectal cancer cells. Expressions of HOTAIR, miRNA-545, and epidermal growth factor receptor (EGFR) mRNA were measured in 100 paired cancerous and non-cancerous tissues as well as in SW480 and LOVO colorectal cancer cell (CRC) lines by quantitative RT-PCR. The relative protein level of EGFR was measured using western blotting. Effects of miRNA-545 and HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches. Insight of mechanism of promotion cancer by miR-545 was gained from luciferase reporter assay and gene expression analysis. CRC proliferation was evaluated using clone formation and MTT assay. Differential expressions of HOTAIR, miR-545, and EGFR were observed in cancerous tissues in comparison to non-cancerous tissues. By expressional management of miR-545, we observed that miR-545 negatively regulated cell proliferation. Also luciferase reporter assay revealed that miR-545 inhibited regulated EGFR expression by affecting its 3'-UTR activity. In addition, miR-545 expression was suppressed by HOTAIR overexpression whereas enhanced by HOTAIR silence. Suppression of EGFR expression by miR-545 mimic was abrogated by HOTAIR overexpression. Monitoring of tumor growth in mice showed that miR-545 overexpression suppressed LOVO tumor growth. Our data suggested that HOTAIR long non-coding RNA mediates microR-545 regulating colorectal cancer cells proliferation.

Sedentary lifestyle related exosomal release of Hotair from gluteal-femoral fat promotes intestinal cell proliferation

Pioneering epidemiological work has established strong association of sedentary lifestyle and obesity with the risk of colorectal cancer, while the detailed underlying mechanism remains unknown. Here we show that Hotair (HOX transcript antisense RNA) is a pro-adipogenic long non-coding RNA highly expressed in gluteal-femoral fat over other fat depots. Hotair knockout in adipose tissue results in gluteal-femoral fat defect. Squeeze of the gluteal-femoral fat induces intestinal proliferation in wildtype mice, while not in Hotair knockout mice. Mechanistically, squeeze of the gluteal-femoral fat induces exosomal Hotair secretion mainly by transcriptional upregulation of Hotair via NFκB. And increased exosomal Hotair in turn circulates in the blood and is partially endocytosed by the intestine, finally promoting the stemness and proliferation of intestinal stem/progenitor cells via Wnt activation. Clinically, obese subjects with sedentary lifestyle have much higher exosomal HOTAIR expression in the serum. These findings establish that sedentary lifestyle promotes exosomal Hotair release from the gluteal-femoral fat, which in turn facilitates intestinal stem and/or progenitor proliferation, raising a possible link between sedentary lifestyle with colorectal tumorigenesis.

HOTAIR functions as a competing endogenous RNA to regulate PTEN expression by inhibiting miR-19 in cardiac hypertrophy.

Sustained cardiac hypertrophy (CH) is related to a variety of physiological as well as pathological stimuli and eventually increases the risk of heart failure. HOTAIR has been identified as a competing endogenous RNA in multiple human biological processes. Whether lncRNA-HOTAIR is involved in the progress of CH and how it works still remain unknown. Herein, we found that HOTAIR was down-regulated, while miR-19 was up-regulated in both heart tissues from TAC-operated mice in vivo and cultural cardiomyocytes treated with Ang-II in vitro by real-time PCR. Meanwhile, HOTAIR expression was negatively correlated with miR-19 in TAC-operated mice. HOTAIR overexpression reduced cell surface area and the expression of hypertrophic markers ANP, BNP, and β-MHC in response to Ang-II stimulation as well as knockdown of miR-19. The further molecular mechanisms of HOTAIR action in CH demonstrated that HOTAIR may act as a competing endogenous RNA (ceRNA) for miR-19, thereby modulating the dis-inhibition of its endogenous target PTEN and playing an important role in inhibiting CH progress. These findings reveal a novel function of LncRNAs, which conduce to an extensive understanding of CH and provide novel research directions and therapeutic options for treating this disease.

HOTAIR upregulates an 18-gene cell cycle-related mRNA network in glioma.

HOTAIR is a tumor promoting long non-coding RNA (lncRNA) with roles in multiple cancers. However, the role of HOTAIR in glioma has not been well charaterized. Genes that positively correlated with HOTAIR were identified from the Chinese Glioma Genome Atlas and constructed into an interacting network. In total, 18genes with P-values <0.01 were further extracted and constructed into a subnetwork. Real-time PCR, western blot and immunofluorescence analyses were employed to examine the expression of the genes after HOTAIR overexpression or knockdown. Intracranial glioblastoma multiform (GBM) models were used to test the potential of HOTAIR as a glioma therapy target. It was discovered that the 18 genes that most significantly correlated with HOTAIR expression formed a cell cycle-related mRNA network, which is positively regulated by HOTAIR. Furthermore, HOTAIR knockdown inhibited mouse intracranial GBM model formation. HOTAIR positively regulates a cell cycle-related mRNA network in glioma, and could be a potential therapeutic target for treating glioma.

Association of TagSNP in lncRNA HOTAIR with susceptibility to noise-induced hearing loss in a Chinese population

BackgroundNoise-induced hearing loss (NIHL) is a multifactorial disease, and dysregulation of oxidative stress is universally acknowledged as one crucial pathogenic factor for this disease. Recently studies have found the LncRNA HOTAIR is involved in the alteration of oxidative stress level, cell proliferation, cell cycle progression, and apoptosis. Considering the effects of lncRNA HOTAIR in cellular oxidative stress, we sought to investigate the influence of lncRNA HOTAIR variants on the risk of NIHL. MethodsTo explore the effects of HOTAIR polymorphisms on individual susceptibility to NIHL, We performed genotyping of three tagSNPs (rs874945, rs4759314 and rs7958904) in HOTAIR gene in a Chinese population which consists of 570 NIHL cases and 570 controls. The luciferase assays were further performed to investigate the regulatory function of HOTAIR tagSNPs. ResultsOur results revealed individuals with the G allele of HOTAIR tagSNP rs4759314 and the haplotype (rs874945, rs4759314 and rs7958904) are associated with an increased risk of NIHL in a Chinese population. Meanwhile, the rs4759314 G allele could significantly increase the expression of lncRNA HOTAIR. ConclusionsThe genetic polymorphism within HOTAIR gene may play a crucial role in the occurrence and development of NIHL.

Study of long non-coding RNA HOTAIR expression in middle ear cholesteatoma

Objective:To discuss the different expression of some long-chain noncoding RNA between middle ear cholesteatoma epithelial tissue and normal external ear canal skin.Method:Real-time quantitative PCR was used to detect the expression of 6 kinds of lncRNA: HOTAIR, ANCR, TINCR, PRINS, BANCR, PICSAR in 25 cases of cholesteatoma epithelial tissues and 15 cases of normal external auditory canal skin tissue samples, respectively. And compared the expression level of lncRNA in patients with different degree of bone destruction.Result:Expression level of HOTAIR was significantly increased in cholesteatoma epithelial tissues compared with the normal external auditory canal skin tissues,and the difference is statistically significant (P< 0.01). While there was no statistically significant difference expression of the rest of the five kinds of lncRNA between middle ear cholesteatoma epithelial tissues and normal external ear canal skin (P> 0.05). And there was no statistically significant difference expression of HOTAIR in patients with different degree of bone destruction (P> 0.05).Conclusion:Expression level of HOTAIR was up-regulated in middle ear cholesteatoma epithelial tissue compared with the normal external auditory canal skin tissues, and the expression level of HOTAIR has no obvious correlation with degree of bone destruction in patients with cholesteatoma.

Knockdown of long non-coding RNA HOTAIR increases miR-454-3p by targeting Stat3 and Atg12 to inhibit chondrosarcoma growth

Current practices for the therapy of chondrosarcoma, including wide-margin surgical resection and chemotherapy, are less than satisfactory. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) have an essential role in the initiation and progression of tumors. As a typical lncRNA, HOTAIR is significantly overexpressed in various tumors. However, the function and potential biological mechanisms of HOTAIR in human chondrosarcoma remain unknown. Quantitative RT-PCR demonstrated that HOTAIR expression was upregulated in chondrosarcoma tissues and cell lines. High HOTAIR expression is correlated with tumor stage and poor prognosis. Functional experiments reveal that HOTAIR knockdown leads to growth inhibition of human chondrosarcoma cells in vitro and in vivo. In addition to cycle arrest and apoptosis, knockdown of HOTAIR inhibits autophagy, which favors cell death. Mechanistically, we demonstrated that HOTAIR induced DNA methylation of miR-454-3p by recruiting EZH2 and DNMT1 to the miR-454-3p promoter regions, which markedly silences miR-454-3p expression. Further analysis revealed that STAT3 and ATG12 are targets of miR-454-3p, initiate HOTAIR deficiency-induced apoptosis and reduce autophagy. Collectively, our data reveal the roles and functional mechanisms of HOTAIR in human chondrosarcoma and suggest that HOTAIR may act as a prognostic biomarker and potential therapeutic target for chondrosarcoma.

Long non-coding RNA HOTAIR promotes expression of ADAMTS-5 in human osteoarthritic articular chondrocytes.

Accumulating evidence indicated that inhibiting the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 ameliorate cartilage degradation, suggesting ADAMTS-5 as an effective target for treating osteoarthritis (OA). A recent study has identified long noncoding RNA (lncRNA) HOTAIR and ADAMTS-5 as the most up-regulated lncRNA and the most upregulated gene, respectively, in human OA cartilage compared with normal cartilage. In the present study, we explored the regulatory effect of HOTAIR on the expression of ADAMTS-5 as well as the underlying mechanisms in human normal and OA articular chondrocytes. We found that human OA articular chondrocytes had significantly higher basal expression levels of HOTAIR and ADAMTS-5 than normal articular chondrocytes. Tumor necrosis factor (TNF)-α significantly enhanced the basal expression of HOTAIR and ADAMTS-5 in OA but not in normal articular chondrocytes. Lentiviral overexpression and knockdown of HOTAIR markedly increased and decreased the expression of ADAMTS-5, respectively, in OA but not in normal articular chondrocytes in the presence or absence of TNF-α. Neither overexpression/ knockdown of HOTAIR nor TNF-α showed a significant effect on the ADAMTS-5 gene promoter in OA articular chondrocytes. Although HOTAIR showed no significant effect on the stability of ADAMTS-5 mRNA in normal articular chondrocytes, HOTAIR overexpression and knockdown respectively increased and decreased the ADAMTS-5 mRNA stability in OA articular chondrocytes. TNF-α enhanced the protective effect of HOTAIR on the ADAMTS-5 mRNA stability. In conclusion, this study provides the first evidence supporting that HOTAIR strongly promotes the expression of ADAMTS-5 by increasing its mRNA stability in human OA articular chondrocytes; this effect is enhanced by TNF-α. It adds new insights into the pathogenesis of OA and suggests that HOTAIR could be a new therapeutic target for ADAMTS-5 inhibition in human OA cartilage.

Long Non-Coding RNA HOTAIR Regulates the Proliferation, Self-Renewal Capacity, Tumor Formation and Migration of the Cancer Stem-Like Cell (CSC) Subpopulation Enriched from Breast Cancer Cells.

PurposeLong non-coding RNAs (lncRNAs) play important roles in the malignant behavior of cancer. HOTAIR, a well-studied lncRNA, contributes to breast cancer development, and overexpression of HOTAIR predicts a poor prognosis. However, the regulatory role of HOTAIR in the cancer stem-like cell (CSC) subpopulation remains largely unknown. Our goal was to determine the regulatory functions of HOTAIR in the processes of self-renewal capacity, tumor formation and proliferation of CSCs derived from breast cancer.MethodsWe first enriched and incubated the CSC population derived from breast cancer cell line MCF7 (CSC-MCF7) or MDA-MB-231 (MB231, CSC-MB231). Self-renewal capacity and tumor formation were assessed in vitro and in vivo to determine the stemness of CSCs. We assessed the impact on ectopically upregulated or downregulated expression of HOTAIR in CSCs by soft agar, self-renewal capacity and CCK-8 assays. The functional domain of HOTAIR was determined by truncation. RT-qPCR and semiquantitative Western blotting were performed to detect the expression levels of genes of interest. Chromatin IP (ChIP) was employed to detect the transcriptional regulatory activity of p53 on its target gene.ResultsAfter the identification of CSC properties, RT-qPCR analysis revealed that HOTAIR, but not other cancer-associated lncRNAs, is highly upregulated in both CSC-MCF7 and CSC-MB231 populations compared with MCF7 and MB231 populations. By modulating the level of HOTAIR expression, we showed that HOTAIR tightly regulates the proliferation, colony formation, migration and self-renewal capacity of CSCs. Moreover, full-length HOTAIR transcriptionally inhibits miR-34a specifically, leading to upregulation of Sox2, which is targeted by miR-34a. Ectopic introduction of miR-34a mimics reverses the effects of HOTAIR on the physiological processes of CSCs, indicating that HOTAIR affects these processes, including self-renewal capacity; these effects are dependent on the regulation of Sox2 via miR-34a. Interestingly, tight transcriptional regulation of p53 by HOTAIR was found; accordingly, p21 is indirectly regulated by HOTAIR, resulting in cell cycle entry.ConclusionThese results suggest that HOTAIR is a key regulator of proliferation, colony formation, invasion and self-renewal capacity in breast CSCs, which occurs in part through regulation of Sox2 and p53.

Prognostic value of abnormally expressed lncRNAs in ovarian carcinoma: a systematic review and meta-analysis.

Ovarian cancer (OC) is the most deadly gynecological cancer and it is urgently needed to find a new marker for the progress of OC. Many long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in ovarian carcinoma, and may serve as prognostic markers. Therefore, we conducted this meta-analysis to gain a better understanding of the prognostic value of lncRNAs in patients with varian carcinoma. We systematically searched PubMed, EMBASE, and Web of Science. A total of 13 eligible studies, including 10 on clinicopathological features, 13 on prognosis were identified. Pooled hazard ratios (HRs) or odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. Our results revealed that the increased expressions of 8 lncRNAs were associated with poor prognosis and the decreased expressions of 5 lncRNAs were related to poor prognosis in ovarian carcinoma. High HOTAIR expression was associated with shorter overall survival in ovarian cancer (pooled HR: 2.05, 95% CI: 1.51-2.77, P < 0.001). In conclusion, our meta-analysis suggested that LncRNAs could function as potential prognostic markers for ovarian cancer patients and high expression HOTAIR was associated with shorter overall survival in ovarian cancer.

Schisandrin B inhibits the proliferation and invasion of glioma cells by regulating the HOTAIR-micoRNA-125a-mTOR pathway.

Glioma is one of the most common malignant central nervous system tumors in humans. Schisandrin B (Sch B) has been confirmed to cause the proliferation and invasion of glioma cells. In the present study, the potential mechanism underlying the antitumor effect of Sch B on glioma cells was investigated. The glioma cell lines, U251 and U87, were exposed to Sch B, and the cell viability, apoptosis, migration, and invasion were determined using the MTT assay, flow cytometry, and transwell assay, respectively. Then, the effects of HOTAIR and miR-125a on tumor biology and the mammalian target of rapamycin (mTOR) protein expression in cell lines exposed to Sch B were investigated. The results showed that Sch B decreased HOTAIR expression and increased miR-125a-5p expression. HOTAIR overexpression decreased miR-125a expression and increased mTOR expression in cells with the treatment of Sch B. The miR-125a inhibitor reversed the effects of HOTAIR downregulation on cell proliferation and migration. On co-incubation with rapamycin, a specific mTOR inhibitor, the cell viability, migration, and invasion were decreased and cell apoptosis was increased in two cell lines exposed to Sch B after the treatment of pcDNA-HOTAIR. In conclusion, Sch B played an inhibitory role in the proliferation and invasion of glioma cells by regulating the HOTAIR-micoRNA-125a-mTOR pathway.

Transcription of HOTAIR is regulated by RhoC-MRTF-A-SRF signaling pathway in human breast cancer cells

HOTAIR is a long non-coding RNA highly expressed in cancer tissues and is a negative prognostic factor, whereas the mechanism by which HOTAIR expression is upregulated in cancers remains elusive. In the present study, the regulation of HOTAIR transcription was investigated in breast cancer cells MCF7 and T47D. We found that, when the RhoC-ROCK signaling was disturbed by specific siRNAs or chemical inhibitors, the expression of HOTAIR would be down-regulated. Further, MRTF-A and SRF were found to affect HOTAIR expression. HOTAIR promoter activity was demonstrated to be regulated by the RhoC-MRTF-A-SRF signaling in a CArG-box-dependent manner. Moreover, MRTF-A was identified to physically interact with HOTAIR promoter, and RNA polymerase II association on HOTAIR promoter was enhanced by MRTF-A overexpression. Taken together, our results suggest that HOTAIR is regulated by the RhoC-MRTF-A-SRF signaling pathway in breast cancer cells.

WITHDRAWN: LncRNA-HOTAIR Activates Tumor Cell Proliferation and Migration by Suppressing MiR-326 in Cervical Cancer.

Cervical cancer is the second most common malignant cancer in females. Recent findings indicate that LncRNA-HOTAIR played a crucial role in tumor progression. In our present study, we aimed to explore the regulating role of HOTAIR in the progression of cervical cancer. The expression of HOTAIR was found up-regulated in cervical cancer tissues and cell lines (Hela, CasKi, Me180 and C-33A) compared with the normal tissues and normal cervical cell line (Ect1/E6E7). To examine the function of HOTAIR, gene knockdown (KD) was performed using HOTAIR short hairpin RNAs (shRNAs). HOTAIR shRNA significantly suppressed cells proliferation and migration in Hela cells. Besides that, the targeting relationship between HOTAIR and miR-326 was firstly revealed by bioinformatics prediction. Simultaneously, suppressed expression of miR-326 was detected in tumor tissues and cell lines compared with the control. Then, suppressed expression level of miR-326 was elevated by adding miR-326 mimic in cervical cancer cells transfected with LncR-HOTAIR. Similarly, increased expression level of miR-326 was reduced by adding miR-326 inhibitor in cervical cancer cells transfected with HOTAIR shRNA. The targeting relationship between HOTAIR and miR-326 was further been confirmed through the luciferase report assay. Moreover, there existed a negative relationship between the expression of HOTAIR and miR-326. In addition, enhanced cell proliferation and migration abilities were suppressed by HOTAIR shRNA in cells transfected with miR-326 inhibitor. Finally, the in vivo experiment revealed that tumor growth and metastasis could also be inhibited by HOTAIR shRNA. Our present study elucidated the regulating role of HOTAIR/miR-326 axis in cervical cancer progression and provided a new potential therapeutic strategy for cervical cancer.

Circulating Long Noncoding RNA HOTAIR is an Essential Mediator of Acute Myocardial Infarction

Background/Aims: Acute myocardial infarction (AMI) is one of the leading causes of death in the world. However, specific diagnostic biomarkers have not been fully determined, and candidate regulatory targets for AMI have not been identified to date. Long noncoding RNAs (lncRNAs) are a class of RNA molecules that have diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases, particularly AMI, is still in its infancy. HOX antisense intergenic RNA (HOTAIR), a 2.2 kb lncRNA, was initially described as a modulator of HOX gene expression. Recent studies have illustrated the important role of HOTAIR in cancer progression, but few studies have reported its function in cardiac disease, including AMI. In the current study, we aimed to detect the expression of HOTAIR during AMI and to explore its function in hypoxia-induced cardiomyocyte injury in neonatal cardiomyocytes. Methods: In 50 consecutively enrolled AMI patients, we examined the serum expression levels of HOTAIR and analysed its correlation with cardiac troponin I (cTnI) expression. Another 50 age- and sex-matched subjects served as healthy controls. Next, the HOTAIR expression was detected in the serum from C57BL/6J mice subjected to coronary artery ligation and in neonatal rat cardiomyocytes induced by hypoxia. Cultured cardiomyocytes apoptosis were measured by terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) staining. A search for miRNAs that had complementary base paring with HOTAIR was performed utilizing an online software program, and the interaction between miR-1 and HOTAIR was examined using a luciferase reporter assay. Results: Our study revealed that HOTAIR expression was significantly decreased in the serum of AMI patients compared with that of the healthy controls. Similarly, we observed that HOTAIR was downregulated in the serum of mice subjected to coronary artery ligation and in cultured cardiomyocytes exposed to hypoxia. Furthermore, we observed that the adenovirus vector-driven overexpression of HOTAIR dramatically limited hypoxia-induced myocyte apoptosis, whereas knockdown HOTAIR by AdshHOTAIR (adenoviral short hairpin HOTAIR) exhibited the opposite phenotype. Mechanistically, we discovered that the cardioprotective function of HOTAIR is partly based on the negative regulation of miR-1. Conclusions: Taken together, the results of our study suggest that HOTAIR is a protective factor for cardiomyocytes and that the plasma concentration of HOTAIR may serve as a biomarker for human AMI diagnosis.

Up-regulated HOTAIR induced by fatty acids inhibits PTEN expression and increases triglycerides accumulation in HepG2 cells

ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation unrelated to excess alcohol intake, in which the hepatic expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is inhibited. Long non-coding RNA HOTAIR suppresses PTEN expression in hepatic stellate cells during liver fibrosis, and it is involved in liver lipid dysregulation. In this study, we evaluated whether the PTEN down-regulation and lipid accumulation in hepatic cells might be mediated by HOTAIR during the development of NAFLD. Free fatty acids (FFAs) treatment promoted triglyceride accumulation in HepG2 cells, significantly increasing HOTAIR expression and inhibiting PTEN expression (both at mRNA and protein levels).The effects on HOTAIR and PTEN expressions disappeared after withdrawal of the FFAs treatment. SiRNA-mediated HOTAIR knockdown prevented PTEN down-regulation and triglyceride accumulation in HepG2 cells treated with FFAs; and CAPE (an NF-κBp65 inhibitor) treatment prevented the HOTAIR up-regulation and PTEN down-regulation. FFAs could induce the up-regulation of HOTAIR in HepG2 cells probably dependent on the NF-κB signaling, and consequently suppress PTEN expression and promote triglyceride accumulation. Aberrant up-regulation of HOTAIR mediated by excessive circulating FFAs levels may be a crucial mechanism associated with liver steatosis.

Tetracycline-controllable artificial microRNA-HOTAIR + EZH2 suppressed the progression of bladder cancer cells.

Previous studies have suggested that EZH2 is up-regulated in bladder cancer tissues and identified it as a biomarker for poor prognosis. However, the biological functions of EZH2 in bladder cancer cells remain unknown. In this research, we discovered that EZH2 expression is irrelevant to the TNM stage and poor prognosis of bladder cancer patients. But suppression of EZH2 can slowdown the progression of bladder cancer cells. Moreover, we used the technology of synthetic biology to construct the tetracycline-controllable artificial microRNA-HOTAIR + EZH2, which can decrease the expression of HOTAIR and EZH2 in a doxycycline dosage-dependent manner. And we also found that HOTAIR expression was positively correlated with EZH2 expression. Tetracycline-controllable artificial microRNA-HOTAIR + EZH2 can inhibit the proliferation and migration of bladder cancer cells. Meanwhile, the apoptosis rate of bladder cancer cells was increased. Taken together, our research showed the cancer-promoting effects of EZH2 and created a novel method to rescue the development of bladder cancer cells.

HOTAIR Long Noncoding RNA is not a Biomarker for Acute Myeloid Leukemia (AML) in Iranian Patients

Accumulating evidence indicates that lncRNAs may have potential as new biomarkers to predict prognosis of different human cancers. HOTAIR lncRNA, transcribed from the human HOX locus, has been suggested to regulate gene expression of important target genes and up-regulation has been noted in malignancies. The role of HOX transcript antisense RNA in acute myeloid leukemia (AML) was investigated in the present case control study. HOTAIR expression was evaluated in blood samples of twenty five de novo AML patients and fifty healthy controls using real-time quantitative reverse transcription-PCR (qRT-PCR). Our results demonstrated no significant differences in HOTAIR lncRNA expression level between AML patients and healthy individuals. The obtained data indicate that HOTAIR is not an informative and reliable biomarker for AML diagnosis, although our results should be confirmed in further studies.

MiR-449 and HDAC modulates HOTAIR Expression which Predicts Poor Prognosis in Resected Gastroesophageal Adenocarcinomas and Doubles Proliferation Rate in HFE145 Cells

miR-449 and HDAC modulates HOTAIR Expression which Predicts Poor Prognosis in Resected Gastroesophageal Adenocarcinomas and Doubles Proliferation Rate in HFE145 Cells

Hotair facilitates hepatic stellate cells activation and fibrogenesis in the liver

Long non-coding RNAs (lncRNAs) are increasingly recognized as major players in regulating various biological processes. LncRNA HOX transcript antisense RNA (Hotair) has been extensively studied in cancer. However, the role of Hotair in liver fibrosis remains unknown. Here we observed that Hotair expression was significantly increased in CCl4-induced mouse liver fibrosis models, human fibrotic livers and activated hepatic stellate cells (HSCs) by TGF-β1 stimulation. Enforced expression of Hotair in LX-2 cells promoted cell proliferation and activation while inhibition of its expression had an opposite effect. Furthermore, we found that Hotair may act as an endogenous ‘sponge’ of miR-148b, which regulates expression of the DNMT1/MEG3/p53 pathways in HSCs. Intriguingly, Hotair enhanced polycomb repressive complex 2 (PRC2) occupancy and histone H3K27me3 repressive marks, specifically at the MEG3 promoter region. Finally, we found that Hotair forms an RNA/DNA hybrid and recruits PRC2 to MEG3 promoter. These data suggest that Hotair inhibition may represent a promising therapeutic option for suppressing liver fibrosis.