Circ_0004104 knockdown alleviates oxidized low-density lipoprotein-induced dysfunction
      in vascular endothelial cells through targeting miR-328-3p/TRIM14 axis in atherosclerosis

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Abstract

Background

Circular RNAs have shown important regulatory roles in cardiovascular diseases, containing atherosclerosis (AS). We intended to explore the role of circ_0004104 in AS using oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cells and its associated mechanism.

Methods

Real-time quantitative polymerase chain reaction and Western blot assay were conducted to analyze RNA levels and protein levels, respectively. Cell viability, apoptosis, angiogenic ability and inflammatory response were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, flow cytometry, capillary-like network formation assay and enzyme-linked immunosorbent assay, respectively. Cell oxidative stress was assessed using commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA-pull down assay were performed to verify the intermolecular interaction.

Results

ox-LDL exposure up-regulated the level of circ_0004104 in HUVECs. ox-LDL exposure suppressed cell viability and angiogenic ability whereas promoted the apoptosis, inflammation and oxidative stress of HUVECs partly through up-regulating circ_0004104. MicroRNA-328-3p (miR-328-3p) was confirmed as a target of circ_0004104. MiR-328-3p interference largely reversed circ_0004104 silencing-mediated effects in HUVECs upon ox-LDL exposure. MiR-328-3p interacted with the 3′ untranslated region of tripartite motif 14, and circ_0004104 positively regulated TRIM14 expression by sponging miR-328-3p. TRIM14 overexpression largely overturned miR-328-3p accumulation-induced influences in HUVECs upon ox-LDL exposure.

Conclusion

Circ_0004104 knockdown attenuated ox-LDL-induced dysfunction in HUVECs via miR-328-3p-mediated regulation of TRIM14.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12872-021-02012-7.

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Most cited references 39

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Natural RNA circles function as efficient microRNA sponges.

Thomas B. Hansen, Trine I. Jensen, Bettina H. Clausen … (2014)

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.

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Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis.

Michael Gimbrone, Guillermo García-Cardeña (2016)

Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell dysfunction, in its broadest sense, encompasses a constellation of various nonadaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment.

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Roles for microRNAs in conferring robustness to biological processes.

Margaret S. Ebert, Phillip A. Sharp (2012)

Biological systems use a variety of mechanisms to maintain their functions in the face of environmental and genetic perturbations. Increasing evidence suggests that, among their roles as posttranscriptional repressors of gene expression, microRNAs (miRNAs) help to confer robustness to biological processes by reinforcing transcriptional programs and attenuating aberrant transcripts, and they may in some network contexts help suppress random fluctuations in transcript copy number. These activities have important consequences for normal development and physiology, disease, and evolution. Here, we will discuss examples and principles of miRNAs that contribute to robustness in animal systems. Copyright © 2012 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Ying Shen:

ORCID: http://orcid.org/0000-0001-9500-2700

mineshenying@163.com

Journal

Journal ID (nlm-ta): BMC Cardiovasc Disord

Journal ID (iso-abbrev): BMC Cardiovasc Disord

Title: BMC Cardiovascular Disorders

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2261

Publication date (Electronic): 23 April 2021

Publication date PMC-release: 23 April 2021

Publication date Collection: 2021

Volume: 21

Electronic Location Identifier: 207

Affiliations

Department of Cardiology, The Puren Hospital, No. 218, Changqing First Road, Jianghan District, Wuhan, 430081 Hubei China

Author information

Ying Shen http://orcid.org/0000-0001-9500-2700

Article

Publisher ID: 2012

DOI: 10.1186/s12872-021-02012-7

PMC ID: 8066471

PubMed ID: 33892646

SO-VID: 6d564c19-aa87-4c9e-896e-6873f774610e

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 27 January 2021

Date accepted : 13 April 2021

Custom metadata

ScienceOpen disciplines: Cardiovascular Medicine

Keywords: atherosclerosis,oxidized low-density lipoprotein,circ_0004104,mir-328-3p,trim14

Data availability:

ScienceOpen disciplines: Cardiovascular Medicine

Keywords: atherosclerosis, oxidized low-density lipoprotein, circ_0004104, mir-328-3p, trim14

Circ_0004104 knockdown alleviates oxidized low-density lipoprotein-induced dysfunction in vascular endothelial cells through targeting miR-328-3p/TRIM14 axis in atherosclerosis

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Abstract

Background

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Supplementary Information

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Karger: Cardiovascular System

Most cited references 39

Natural RNA circles function as efficient microRNA sponges.

Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis.

Roles for microRNAs in conferring robustness to biological processes.

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