Long Noncoding RNA HOXA-AS3 Integrates NF-<i>κ</i>B Signaling To Regulate Endothelium Inflammation

Zhu, Xinxing; Chen, Du-Chu; Li, Yanli; Yu, Jinjin; Qiao, Liang; Lin, Shuibin; Chen, Demeng; Zhong, Genshen; Lu, Xifeng; Wang, Yi–Ze; Wen, Jieqi; Zhong, Xinqi; Jiang, Yi‐Zhou

doi:10.1128/mcb.00139-19

Cited by 25 publications

(24 citation statements)

References 46 publications

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“…In the current study, we identified a novel lncRNA, HOXA cluster antisense RNA 3 (HOXA‐AS3). It was found to be one of the most up‐regulated lncRNAs in GBM tissues 10,11 . HOXA‐AS3 is a HOX cluster, and it is a set of transcription factor genes that regulate hematopoietic lineage differentiation and embryological development 10,12 .…”

Section: Introductionmentioning

confidence: 99%

“…It was found to be one of the most up-regulated lncRNAs in GBM tissues. 10,11 HOXA-AS3 is a HOX cluster, and it is a set of transcription factor genes that regulate hematopoietic lineage differentiation and embryological development. 10,12 Members of the HOX cluster family, such as HOXA-AS2, have been shown to regulate cell proliferation and the formation of tumour-related vasculogenic mimicry in various tumours.…”

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confidence: 99%

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LncRNA HOXA‐AS3 promotes the malignancy of glioblastoma through regulating miR‐455‐5p/USP3 axis

Chen

Zhang

et al. 2020

J Cellular Molecular Medi

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Glioblastoma multiforme (GBM) is a fast-growing type of aggressive and lethal primary brain tumour. 1,2 Because the pathologic mechanisms of GBM are not fully understood, more research is needed to identify effective predictive biomarkers and therapeutic targets for GBM. 2,3 Emerging studies, supported by whole-genome sequencing technology and microarray assays, have shown long non-coding RNAs (lncRNAs) to be key regulatory transcripts. 4 LncRNAs are classified

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

LncRNA HOXA‐AS3 promotes the malignancy of glioblastoma through regulating miR‐455‐5p/USP3 axis

Chen

Zhang

et al. 2020

J Cellular Molecular Medi

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“…All of the 39 Hox genes are classified into four clusters, namely HoxA, HoxB, HoxC, HoxD respectively (Bhatlekar et al, 2014). Among the four clusters, HoxA cluster has attracted increasing attention because of its critical regulatory role in development of cardiovascular diseases, such as cardiac morphogenesis, ventricular septal defects, and endothelial inflammation (Di-Poi et al, 2010;Zhu et al, 2019a;Zhu et al, 2019b;Beachy et al, 2013;Makki and Capecchi, 2012). Recent studies have revealed that HoxA9, a member of HoxA cluster genes, was downregulated in hypertensive patients (Pirro et al, 2007), and that mRNA level of HoxA9 was enhanced in cardiac hypertrophy (Zhou et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

PRMT5 Prevents Cardiomyocyte Hypertrophy via Symmetric Dimethylating HoxA9 and Repressing HoxA9 Expression

Cai¹,

Liu²,

Wang³

et al. 2020

Front. Pharmacol.

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The present study reveals a link between protein arginine methyltransferase 5 (PRMT5) and Homebox A9 (HoxA9) in the regulation of cardiomyocyte hypertrophy. In cardiomyocyte hypertrophy induced by β-adrenergic receptor agonist isoprenaline (ISO), PRMT5 expression was decreased while HoxA9 was upregulated. Silencing of PRMT5 or inhibition of PRMT5 by its pharmacological inhibitor EPZ augmented the expressions of cardiomyocyte hypertrophic genes brain natriuretic peptide (BNP) and β-Myosin Heavy Chain (β-MHC), whereas overexpression of PRMT5 inhibited ISO-induced cardiomyocyte hypertrophy, suggesting that PRMT5 ameliorates cardiomyocyte hypertrophy. On the contrary, HoxA9 promoted cardiomyocyte hypertrophy, as implied by the gain-of-function and loss-of-function experiments. HoxA9 was involved in the regulation of PRMT5 in cardiomyocyte hypertrophy, since HoxA9 knockdown prevented si-RPMT5-induced cardiomyocyte hypertrophy, and HoxA9 expression impaired the anti-hypertrophic effect of PRMT5. Co-immunoprecipitation experiments revealed that there were physical interactions between PRMT5 and HoxA9. The symmetric dimethylation level of HoxA9 was decreased by ISO or EPZ treatment, suggesting that HoxA9 is methylated by PRMT5. Additionally, PRMT5 repressed the expression of HoxA9. Chromatin immunoprecipitation (ChIP) assay demonstrated that HoxA9 could bind to the promoter of BNP, and that this binding affinity was further enhanced by ISO or EPZ. In conclusion, this study suggests that PRMT5 symmetric dimethylates HoxA9 and represses HoxA9 expression, thus impairing its binding to BNP promoter and ultimately protecting against cardiomyocyte hypertrophy. These findings provide a novel insight of the mechanism underlying the cardiac protective effect of PRMT5, and suggest potential therapeutic strategies of PRMT5 activation or HoxA9 inhibition in treatment of cardiac hypertrophy.

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“…NF-κB signaling is a central mediator of GC progression [25]. HOXA-AS3 is able to colocalize with NF-κB in the promoter region of certain genes, and can directly interact with this transcription factor in order to enhance its activation by regulating IκBα expression and p65 subunit K310 acetylation status [17]. As such, we speculated that HOX-AS3 may drive GC progression via the activation of NF-κB.…”

Section: Discussionmentioning

confidence: 99%

“…In previous reports, HOXA-AS3 has been shown to positively regulate NF-κB signaling by interacting with this transcription factor [17], and abnormal NF-κB signaling can promote GC progression [18][19][20]. As such, we evaluated the ability of HOXA-AS3 to modulate NF-κB signaling in our GC model system.…”

Section: Hoxa-as3 Modulates Nf-κb Signaling To Regulate Gc Cell Biologymentioning

confidence: 97%

LncRNA HOXA-AS3 Promotes Gastric Cancer Progression by Regulating miR-29a-3p/LTβR and Activating NF-κB Signaling

Feng

Zhu

et al. 2020

Preprint

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Background: Gastric cancer (GC) is among the most common and deadliest cancers globally. While many long non-coding RNAs (lncRNAs) are key regulators of GC pathogenesis, the role of HOXA-AS3 in this oncogenic context remains to be defined. Methods: Levels of HOXA-AS3 expression in GC were quantified, after which the functional role of this lncRNA in vitro and in vivo was assessed via HOXA-AS3 knockdown. The localization of HOXA-AS3 within cells was also confirmed, and predicted microRNA (miRNA) targets of this lncRNA and its ability to modulate downstream NF-κB signaling in GC cells were evaluated.Results: GC cells and tissues exhibited significant HOXA-AS3 upregulation (P<0.05), and the levels of this lncRNA were found to be correlated with tumor size, lymph node status, invasion depth, and Helicobacter pylori infection status. Knocking down HOXA-AS3 disrupted GC cell migration, proliferation, and invasion in vitro and tumor metastasis in vivo. At a mechanistic level, we found that HOXA-AS3 was able to sequester miR-29a-3p, thereby regulating the expression of LTβR and modulating NF-κB signaling in GC. Conclusion: HOXA-AS3/miR-29a-3p/LTβR/NF-κB regulatory axis contributes to the progression of GC, thereby offering novel target for the prognosis and treatment of GC.

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Long Noncoding RNA HOXA-AS3 Integrates NF-κB Signaling To Regulate Endothelium Inflammation

Cited by 25 publications

References 46 publications

LncRNA HOXA‐AS3 promotes the malignancy of glioblastoma through regulating miR‐455‐5p/USP3 axis

LncRNA HOXA‐AS3 promotes the malignancy of glioblastoma through regulating miR‐455‐5p/USP3 axis

PRMT5 Prevents Cardiomyocyte Hypertrophy via Symmetric Dimethylating HoxA9 and Repressing HoxA9 Expression

LncRNA HOXA-AS3 Promotes Gastric Cancer Progression by Regulating miR-29a-3p/LTβR and Activating NF-κB Signaling

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