Multi-Omics Approaches to Study Long Non-coding RNA Function in Atherosclerosis

Turner, Adam; Wong, Doris; Khan, Mohammad Daud; Dreisbach, Caitlin; Palmore, Meredith; Miller, Clint L.

doi:10.3389/fcvm.2019.00009

Cited by 34 publications

(24 citation statements)

References 224 publications

(225 reference statements)

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“…The complexity of its causes and mechanisms makes ATH prevention and treatment largely ineffective, becoming an enormous challenge for our society, favored by our lifestyle [2,3]. Thus, there is an urgent need to develop a more personalized medicine, and to enhance patient care through improved diagnostic sensitivity with more effective interventions in ATH prevention and treatment [4]. In this sense, years of research on the genomic basis of ATH have provided the biomedical community with a knowledge of gene‐related ATH risk factors, such as SNPs [5,6], genes and gene variants [7–9], alterations in DNA methylation [10,11], changes in gene expression [12,13], etc.…”

Section: Background Atherosclerosis Progression and The Dark Transcrmentioning

confidence: 99%

“…High‐throughput sequencing has allowed an exponential growth in the amount of sequence data generated in large number of individuals, and expanded the number of non‐coding RNA (ncRNA) transcripts predicted to play a critical role in the pathogenesis of ATH [4] (Table 3), although because of their low expression levels, the study of lncRNAs is actually so challenging that many of them still remain poorly characterized and annotated. The lncRNA more clearly associated to ATH pathogenesis is CDKN2B‐AS1, also known as ANRIL (Antisense Non‐coding RNA in the INK4 locus) (see [1] for a recent review), that it is transcribed from chromosome 9p21 and acts as a lncRNA‐guide to localize the polycomb repressive complex (PRC) at target promotors through a direct interaction with its subunits CBX7 or SUZ12 [154].…”

Section: Long Non‐coding Rnas (Lncrnas) and Their Functional Relationmentioning

confidence: 99%

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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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Section: Background Atherosclerosis Progression and The Dark Transcrmentioning

confidence: 99%

Section: Long Non‐coding Rnas (Lncrnas) and Their Functional Relationmentioning

confidence: 99%

Unveiling ncRNA regulatory axes in atherosclerosis progression

Navarro

Mallén

Cruzado

et al. 2020

Clinical & Translational Med

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“…The molecular mechanism underlying atherosclerosis is not completely understood; however, numerous studies have indicated that lncrnas serve pivotal roles in the pathological processes of atherosclerosis (7)(8)(9)(10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

“…Pad frequently occurs in the arteries of the lower extremities and occlusive atherosclerosis impairs the blood supply to the lower extremities (6). accumulating evidence has revealed that a variety of long non-coding rnas (lncrnas) participate in the onset and progress of atherosclerosis, and are involved in multiple pathological processes and signaling pathways, suggesting that lncrnas may serve a vital role in atherosclerosis (7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Antisense long non‑coding RNA WEE2‑AS1 regulates human vascular endothelial cell viability via cell cycle G2/M transition in arteriosclerosis obliterans

et al. 2020

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long non-coding rnas (lncrnas) affect atherosclerosis by regulating the physiological and pathological processes of endothelial cells; however, the role of lncrna Wee2 antisense rna 1 (Wee2-aS1) in arteriosclerosis obliterans (aSo) is not completely understood. The present study aimed to explore the function of lncrna Wee2-aS1 in human vascular endothelial cells. The results indicated that lncRNA WEE2-AS1 was significantly elevated in plasma and artery tissue samples of patients with aSo compared with healthy controls. The fluorescence in situ hybridization results suggested that lncrna Wee2-aS1 was expressed in the cytoplasm and nuclei of primary human umbilical vein endothelial cells (HuVecs). The cell counting Kit-8 assay results suggested that lncrna Wee2-aS1 knockdown significantly promoted HuVec viability, whereas lncrna Wee2-aS1 overexpression inhibited HuVec viability compared with the negative control groups. Furthermore, analysis of the cell cycle by flow cytometry indicated that lncRNA WEE2-AS1 knockdown significantly decreased the proportion of cells in the G 0 /G 1 phase and significantly increased the proportion of cells in the G 2 /M phase compared with the negative control group. However, lncRNA WEE2-AS1 overexpression had no significant effect on cell cycle distribution compared with the negative control group. The western blotting results indicated that lncrna WEE2-AS1 knockdown significantly reduced the expression levels of phosphorylated cyclin dependent kinase 1, Wee1 homolog 2 and myelin transcription factor 1, but increased the expression level of cell division cycle 25B compared with the negative control group. lncrna Wee2-aS1 overexpression displayed the opposite effect on protein expression. collectively, the present study suggested that lncrna WEE2-AS1 was significantly upregulated in ASO and may serve a role in regulating human vascular endothelial cell viability. Further investigation into lncrna Wee2-aS1 may broaden the current understanding of the molecular mechanism underlying ASO, and aid with the identification of specific probes and precise targeted drugs for the diagnosis and treatment of aSo.

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“…AS is commonly recognized as a lipid-induced chronic in ammation of the vascular wall associated with activation and dysfunction of resident vascular cells [4], it contributes to stenosis of internal artery due to plaque accumulation [5]. Number of lncRNAs was reported to implicate in regulating cholesterol and lipid metabolism, they also play diverse roles in a variety of atherosclerotic processes including cell proliferation, migration, in ammation differentiation, and apoptosis [6].…”

Section: Introductionmentioning

confidence: 99%

LncRNA SNHG12 promotes proliferation and migration of vascular smooth muscle cells via targeting miR-766-5p/ EIF5A

Liu

Che

et al. 2020

Preprint

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Background Although lncRNAs have reported to serve as potential biomarkers of atherosclerosis (AS), the role of lncRNA SNHG12 in AS are still unknown. Methods In present study, we investigated the regulatory effects of SNHG12 on human vascular smooth muscle cells (hVSMCs). RT-qPCR were employed to determine the expressions of SNHG12, miR-766-5p and eukaryotic translation initiation factor 5A (EIF5A). Cell viability was estimated via the Cell Counting Kit-8 assay. Wound healing and Transwell invasion assays were used for evaluation of hVSMCs migratory capacity. To further investigate the regulatory mechanisms, binding sites between SNHG12 and miR-766-5p, EIF5A and miR-766-5p were speculated via starBase V2.0, and validated using luciferase reporter gene assay. Results It was identified that SNHG12 was up-regulated in oxidized low-density lipoprotein (ox-LDL)-insulted hVSMCs. Silencing SNHG12 inhibited ox-LDL-induced proliferation and migration of hVSMCs. Moreover, we found that SNHG12 acted as a sponge of miR-766-5p, and miR-766-5p also interacted with EIF5A. EIF5A plasmids promoted the proliferation and migratory capacities of hVSMCs, however, shRNA-SNHG12 counteracted the facilitation of EIF5A plasmids on biological behaviors of hVSMCs. Conclusions These findings of this study demonstrated that SNHG12 facilitated the migration and invasion of hVSMCs via targeting miR-766-5p/EIF5A axis.

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Multi-Omics Approaches to Study Long Non-coding RNA Function in Atherosclerosis

Cited by 34 publications

References 224 publications

Unveiling ncRNA regulatory axes in atherosclerosis progression

Unveiling ncRNA regulatory axes in atherosclerosis progression

Antisense long non‑coding RNA WEE2‑AS1 regulates human vascular endothelial cell viability via cell cycle G2/M transition in arteriosclerosis obliterans

LncRNA SNHG12 promotes proliferation and migration of vascular smooth muscle cells via targeting miR-766-5p/ EIF5A

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