HOTAIR, a long non-coding RNA driver of malignancy whose expression is activated by FOXC1, negatively regulates miRNA-1 in hepatocellular carcinoma

Su, Dong-Na; Wu, Sihan; Chen, Hongtao; He, Jinhua

doi:10.3892/ol.2016.5127

Cited by 53 publications

(46 citation statements)

References 43 publications

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“…The mechanism of this feedback loop was explored in the present study, and it was observed that miR-1 regulates the expression of HOTAIR by directly binding to target sites within the HOTAIR sequence. This is consistent with results in hepatocellular carcinoma [38]. All these data suggest that HOTAIR can bind miR-1 and subsequently contributes to the regulation of AMI.…”

Section: Discussionsupporting

confidence: 80%

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

Gao¹,

Liu²,

Guo³

et al. 2017

Cell Physiol Biochem

123

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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.

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Section: Discussionsupporting

confidence: 80%

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

Gao¹,

Liu²,

Guo³

et al. 2017

Cell Physiol Biochem

123

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“…A significant number of lncRNAs have been identified to be able to participate in metastasis and proliferation regulation by interacting with miRNA, such as HOTAIR (HOX antisense intergenic RNA) [35, 36] and XIST (X-inactive specific transcript) [37, 38]. In this study, we found that CRNDE was highly expressed in colorectal cancer tissue and colorectal cancer cells, while miR-217 expression was low in colorectal cancer tissue and colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 50%

The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway

et al. 2017

Cell Physiol Biochem

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Background/Aims: The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In the present study, we investigated whether CRNDE was involved in the development of colorectal cancer via the binding of microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) to enhance the Wnt signaling pathway. Methods: Quantitative polymerase chain reaction was used to detect CRNDE, miR-217 and TCF7L2 in colorectal cancer tissues and cells. The CCK-8 assay, wound healing assay, and Transwell assay were used to detect cell proliferation, migration and invasion, respectively. Western blotting and luciferase activity assays were used to identify CRNDE and TCF7L2 as one of the direct targets of miR-217. The activity of the Wnt/β-catenin signaling pathway was analyzed by the TOPflash assay, and the subcellular localization of β-catenin and TCF7L2 was analyzed by western blotting and confocal microscopy. Results: In this study, we found that high expression of CRNDE is negatively correlated with low expression of miR-217 in colorectal cancer tissue and colorectal cancer cells. The dual luciferase reporter analysis showed that miR-217 is bound to CRNDE and TCF7L2 and negatively regulate their expression. CRNDE down-regulation inhibited the cell proliferation, migration and invasion in vitro and in vivo and the inhibitions were both completely blocked after miR-217 inhibition or TCF7L2 overexpression. Finally, TOPflash analysis showed that the activity of Wnt/β-catenin signaling is inhibited by CRNDE down-regulation and rescued by TCF7L2 over-expression. Consistently immunostaining and western blotting analysis showed that the expression of b-catenin and TCF7L2 in the nucleus was significantly decreased by CRNDE down-regulation and was rescued by TCF7L2 over-expression. Conclusions: The present study suggest that CRNDE involves in the cell proliferation, migration and invasion of colorectal cancer cells via increasing the expression of TCF7L2 and activity of Wnt/β-catenin signaling through binding miR-217 competitively.

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“…High expression of HOTAIR in HCC tissues and cells was observed in multiple studies . In vivo experiments revealed that the overexpression of HOTAIR can effectively promote HepG2 cell growth . The knockdown of HOTAIR inhibited cell proliferation and induced G0/G1 cell cycle arrest in Huh7 hepatocellular carcinoma cells .…”

Section: Discussionmentioning

confidence: 96%

SNP‐SNP and SNP‐environment interactions of potentially functional HOTAIR SNPs modify the risk of hepatocellular carcinoma

Zhang¹,

Liu²,

Lin³

et al. 2019

Molecular Carcinogenesis

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HOX transcript antisense intergenic RNA (HOTAIR) has been widely regarded as a functional lncRNA contributing to multiple cancers. However, few studies have examined the effect of single nucleotide polymorphisms (SNPs) in HOTAIR on the occurrence and development of hepatocellular carcinoma (HCC). In this study, three potentially functional HOTAIR SNPs (rs17105613, rs12427129, and rs3816153) were selected using bioinformatic tools. A case‐control study including 1262 cases and 1559 controls was conducted to explore the association of HOTAIR SNPs with the risk of HCC in a Southern Chinese population. We found that SNPs rs12427129 and rs3816153 were associated with the risk of HCC in dominant genetic models (CC: CT + TT, adjusted odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.57–0.90 and GG: GT + TT, adjusted OR = 1.30, 95%CI = 1.08–1.57). Additionally, SNP–environment interactions for rs12427129, rs3816153, and HBsAg status were found to enhance the risk of HCC, with FDR‐P as an additive interaction equal to 0.0006 and 0.0144, respectively. In multifactor dimensionality reduction (MDR) analysis, the three‐factor model (HBsAg status, rs12427129 and rs3816153) yielded the highest test accuracy of 77.74% (permutation P < 0.001). Interestingly, the effect of rs12427129 and rs3816153 on the risk of HCC could be modified by HBsAg status, while the rs12427129 CT/TT genotype could antagonize the detrimental effect of rs3816153 GT/TT genotype on HCC. Our findings suggest that rs12427129 and rs3816153, including their SNP‐SNP and SNP‐environment interaction with HBsAg status, potentially play important roles on the susceptibility to HCC.

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HOTAIR, a long non-coding RNA driver of malignancy whose expression is activated by FOXC1, negatively regulates miRNA-1 in hepatocellular carcinoma

Cited by 53 publications

References 43 publications

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

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

The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway

SNP‐SNP and SNP‐environment interactions of potentially functional HOTAIR SNPs modify the risk of hepatocellular carcinoma

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