Uncovering novel landscape of cardiovascular diseases and therapeutic targets for cardioprotection via long noncoding RNA–miRNA–mRNA axes

He, Liang; Chen, Yan; Hao, Shuqing; Qian, Jinqiao

doi:10.2217/epi-2017-0176

Cited by 56 publications

(33 citation statements)

References 67 publications

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“…LncRNAs have emerged as important regulators in various pathological processes that contribute to the development of several diseases . Some lncRNAs are also involved in the development of CVDs, including heart failure, cardiac hypertrophy, cardiometabolic diseases, and myocardial infarction . Various lncRNAs have been shown to control the functions of vascular smooth muscle cells, endothelial cells and macrophages .…”

Section: Introductionmentioning

confidence: 99%

KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS are promising novel biomarkers for diagnosis of coronary artery disease

Zhang

Wang

et al. 2019

Clin Exp Pharma Physio

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This study aimed to evaluate the potential of long noncoding RNAs (lncRNAs) as biomarkers for coronary artery disease (CAD). We measured the levels of three atherosclerosis‐ or cardiac‐related lncRNAs in peripheral blood monocyte cells (PBMCs) from 20 CAD patients and 20 non‐CAD control participants using real‐time reverse transcription–polymerase chain reaction (real‐time RT–PCR) methods. We found that the levels of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), hypoxia‐inducible factor 1 alpha‐antisense RNA 2 (HIF1A‐AS2) and apolipoprotein A‐1 antisense RNA (APOA1‐AS) were significantly increased in CAD patients (KCNQ1OT1 increased by 2.38‐fold, P = 0.00042; HIF1A‐AS2 increased by 2.00‐fold, P = 0.0001; APOA1‐AS increased by 4.52‐fold, P = 0.000048). The area under the ROC curve was 0.865 for KCNQ1OT1, 0.852 for HIF1A‐AS2, and 0.967 for APOA1‐AS. Furthermore, the combination of lncRNAs resulted in a much higher AUC value of 0.990 for the prediction of CAD. Spearman's correlation analysis showed that APOA1‐AS was positively correlated with NT‐proBNP, CKMB, MYO and HsTnT, whereas HIF1A‐AS2 was correlated with NT‐proBNP and HsTnT. Hence, the elevation of KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS predicts CAD and these molecules may be considered as novel biomarkers of CAD.

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Section: Introductionmentioning

confidence: 99%

KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS are promising novel biomarkers for diagnosis of coronary artery disease

Zhang

Wang

et al. 2019

Clin Exp Pharma Physio

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“…Despite its non-coding characteristic, lncRNA has shown various biological activities, and the most important one is to combine with microRNA, also known as sponge function, and competing for endogenous RNAs (ceRNA) [25]. The first step to determine the key lncRNA is to find the differentially expressed lncRNAs.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Long noncoding RNA Oprm1 Attenuates Myocardial Ischemia/Reperfusion Injury by Increasing Endogenous Hydrogen Sulfide Production via Oprm1/miR-30b-5p/CSE axis

Hu¹,

Liu²,

Wu³

et al. 2020

Preprint

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Background: Ischemia/Reperfusion (I/R) Injury largely limits the efficacy of revascularization in acute myocardial infarction. Long noncoding RNA (lncRNA) Oprm1 is protective in cerebral I/R injury. However, the effect of lncRNA Oprm1 on myocardial I/R injury and its mechanism remains unknown.Methods: We ligated and then released the left anterior descending coronary artery of adult male rats to build the I/R model in vivo, while an H9c2 cardiomyocytes hypoxia-reoxygenation (H/R) model was also used. Myocardial infarction area, cardiac function, histology, Tunnel staining, cell viability, and vital protein expression was conducted and compared.Results: lncRNA Oprm1 was significantly down-regulated in the I/R injury model. When administered with the AAV9-Oprm1 vector, the myocardial injury and cardiac function were mitigated and preserved, with apoptosis reduced. The cystathionine-γ-lyase (CSE) expression and hydrogen sulfide (H2S) expression were increased. The dual-luciferase reporter gene revealed the targeted relationship between lncRNA Oprm1 and miR-30b-5p. In H9c2 cardiomyocytes models, the miR-30b-5p blocked the protective effect of lncRNA Oprm1 on H/R injury, when Bcl-2, Bcl-xl was down-regulated, and HIF-1α, Bnip-3, Caspase-3, and Caspase-9 up-regulated.Conclusions: lncRNA Oprm1can competitively combines with miR-30b-5p, which down-regulates the expression of CSE. When administered with lncRNA Oprm1, increased endogenous H2S can reduce apoptosis and protect the myocardium from I/R injury via activating PI3K/Akt pathway and inhibiting HIF1-α activity.

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“…Furthermore, information on the function of individual lncRNAs is scant and incomplete for most of them, since only a few hundreds of lncRNAs have been yet functionally characterized, and for most of them the detailed mechanisms of action are still to be determined. Nevertheless, a number of groups have reported mutual miRNA:mRNA:lncRNA interactions in the context of ATHp ( [248,249] and see Table 3).…”

Section: Unveiling Rna: Rna Regulatory Network In the Progression Ofmentioning

confidence: 99%

Unveiling ncRNA regulatory axes in atherosclerosis progression

Navarro

Mallén

Cruzado

et al. 2020

Clinical & Translational Med

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Completion of the human genome sequencing project highlighted the richness of the cellular RNA world, and opened the door to the discovery of a plethora of short and long non‐coding RNAs (the dark transcriptome) with regulatory or structural potential, which shifted the balance of pathological gene alterations from coding to non‐coding RNAs. Thus, disease risk assessment currently has to also evaluate the expression of new RNAs such as small micro RNAs (miRNAs), long non‐coding RNAs (lncRNAs), circular RNAs (circRNAs), competing endogenous RNAs (ceRNAs), retrogressed elements, 3′UTRs of mRNAs, etc. We are interested in the pathogenic mechanisms of atherosclerosis (ATH) progression in patients suffering Chronic Kidney Disease, and in this review, we will focus in the role of the dark transcriptome (non‐coding RNAs) in ATH progression. We will focus in miRNAs and in the formation of regulatory axes or networks with their mRNA targets and with the lncRNAs that function as miRNA sponges or competitive inhibitors of miRNA activity. In this sense, we will pay special attention to retrogressed genomic elements, such as processed pseudogenes and Alu repeated elements, that have been recently seen to also function as miRNA sponges, as well as to the use or miRNA derivatives in gene silencing, anti‐ATH therapies. Along the review, we will discuss technical developments associated to research in lncRNAs, from sequencing technologies to databases, repositories and algorithms to predict miRNA targets, as well as new approaches to miRNA function, such as integrative or enrichment analysis and their potential to unveil RNA regulatory networks.

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Uncovering novel landscape of cardiovascular diseases and therapeutic targets for cardioprotection via long noncoding RNA–miRNA–mRNA axes

Cited by 56 publications

References 67 publications

KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS are promising novel biomarkers for diagnosis of coronary artery disease

KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS are promising novel biomarkers for diagnosis of coronary artery disease

Overexpression of Long noncoding RNA Oprm1 Attenuates Myocardial Ischemia/Reperfusion Injury by Increasing Endogenous Hydrogen Sulfide Production via Oprm1/miR-30b-5p/CSE axis

Unveiling ncRNA regulatory axes in atherosclerosis progression

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