A Novel circUBR4/miR-491-5p/NRP2 ceRNA Network Regulates Oxidized Low-density Lipoprotein-induced Proliferation and Migration in Vascular Smooth Muscle Cells

Peng, Huaiyu; Liu, Shunfan; Li, Yang; Wang, Chengyang; Zhong, Yang

doi:10.1097/fjc.0000000000001204

Cited by 6 publications

(7 citation statements)

References 39 publications

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“…Moreover, reduced expression of miR-140-5p but enhanced miR-424(322) and miR-146-5p expression can be detected in whole blood samples from PAH patients, suggesting their diagnostic significance (113,114,116). Additionally, circ-UBR4 and miR-29a, as diagnostic biomarkers, are increased in serum from atherosclerosis patients (75,(77)(78)(79)82).…”

Section: Diagnostic Indicators Of the Ups Involving Ncrnasmentioning

confidence: 97%

“…This is particularly noteworthy that circRNA, as an emerging ncRNA, has received much attention in recent years. The mechanism is that circRNAs are involved in CVD progression by sponging miRNAs and regulating downstream proteins (circRNA/miRNA/ubiquitin ligase or deubiquitinating enzymes/ protein axis) via ubiquitination, for example, circDLGAP4/miR-143/HECTD1 axis improved stroke (89), circ-UBR4/miR-637/ FOXO4, circ-UBR4/miR-107/ROCK1, circ-UBR4/miR-491-5p/ NRP2, circ-UBR4/miR-185-5p/FRS2, and circ-CHFR/miR-214-3p/PAPPA axes as well as inhibition of circ_USP36/miR-197-3p/ROBO1 axis could ameliorate atherosclerosis (75)(76)(77)(78)(79)(80)(81), circ-HECTD1/miR-133b/TRAF3 and circ_HECTD1/miR-27a-3p/ FSTL1 axes as well as inhibition of circNfix/Nedd4l/Ybx1 and circNfix/miR-214/Gsk3b axes could reduce myocardial infarction and CVD (49,94,95), circ-sh3rf3/sh3rf3/GATA-4/miR-29a alleviated cardiac fibrosis (71). On the second level, some ubiquitin ligase mimics or inhibitors serve as therapeutic targets, providing new perspectives for the treatment of CVDs.…”

Section: Therapeutic Target Of Ups and Ncrnasmentioning

confidence: 99%

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Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

You,

Wen,

Tian

et al. 2024

Front. Immunol.

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Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin–proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers’ attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.

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Section: Diagnostic Indicators Of the Ups Involving Ncrnasmentioning

confidence: 97%

Section: Therapeutic Target Of Ups and Ncrnasmentioning

confidence: 99%

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

You,

Wen,

Tian

et al. 2024

Front. Immunol.

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“…Previous studies have reported decreased expression of miR‐491‐5p in atherosclerotic plaque tissues and serum samples from patients with AS 19,20 . miR‐491‐5p exerts a protective role in AS development by inhibiting the oxidative stress and inflammatory responses of THP‐1 macrophages via MMP‐9 and suppressing the cellular proliferation and migration of vascular smooth muscle cells 19–22 . A recent study revealed that miR‐491‐5p is associated with the protective effect of circ_0003204 gene silencing on ox‐LDL‐induced HUVECs injury 23 .…”

Section: Introductionmentioning

confidence: 99%

“…19,20 miR-491-5p exerts a protective role in AS development by inhibiting the oxidative stress and inflammatory responses of THP-1 macrophages via MMP-9 and suppressing the cellular proliferation and migration of vascular smooth muscle cells. [19][20][21][22] A recent study revealed that miR-491-5p is associated with the protective effect of circ_0003204 gene silencing on ox-LDL-induced HUVECs injury. 23 Thus, miR-491-5p may exert a protective role in AS development, however, the mechanisms underlying its actions remain to be identified.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of ox‐LDL‐induced endothelial cell injury by LINC02381 knockdown through the microRNA‐491‐5p/transcription factor 7 axis

Zhu

Chen

2023

Immunity Inflam & Disease

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Atherosclerosis (AS) is a complex multifactorial and chronic inflammatory vascular disease that contributes to the development of cardiovascular diseases. Abnormal cellular proliferation in human umbilical vein endothelial cells (HUVECs) is a crucial element in AS development. In this study, we investigated the potential role of the long noncoding RNA LINC02381/ microRNA (miR)-491-5p/transcription factor 7 (TCF7) axis in regulating HUVEC injury in 30 participants suffering from AS and 30 healthy control participants. We established an in vitro model of AS in HUVECs using oxidized low-density lipoprotein (ox-LDL), and measured cellular mRNA and protein levels of LINC02381, miR-491-5p, and TCF7 in serum samples using reverse transcription-quantitative polymerase chain reaction and Western blotting assays. We evaluated cell viability, apoptosis, and inflammation using Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays, respectively. Moreover, we analyzed apoptosis-related protein expression using western blotting analysis and determined the association between miR-491-5p and LINC02381 or TCF7 using dual-luciferase reporter assay, RNA pull-down, and rescue experiments. We observed that LINC02381 was elevated, while miR-491-5p was downregulated in serum samples from participants with AS and in ox-LDL-treated HUVECs. LINC02381 knockdown was protective against HUVEC injury via miR-491-5p inhibition, which is its downstream target. Rescue experiments further demonstrated that miR-491-5p alleviated HUVEC injury by modulating TCF7. Thus, LINC02381 knockdown ameliorated HUVEC injury by regulating the miR-491-5p/TCF7 axis, which provides new insights into AS treatment strategies.

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“…4,5 Vital modulators of ox-LDL-evoked VSMC migration and proliferation, including circular RNAs (cir-cRNAs) and proteins, are under exploration for the moment. 4,6,7 Elucidating the functions of these regulatory molecules will provide a new opportunity for developing better interventions in AS.…”

Section: Introductionmentioning

confidence: 99%

Regulation of oxidized LDL-induced proliferation and migration in human vascular smooth muscle cells by a novel circ_0007478/miR-638/ROCK2 ceRNA network

Guan

Sun

et al. 2023

Vasc Med

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Background: Circular RNAs (circRNAs) have been implicated in the pathogenesis of atherosclerosis (AS) and the migration and proliferation of vascular smooth muscle cells (VSMCs) under oxidized low-density lipoprotein (ox-LDL). Here, we defined the exact action of human circ_0007478 in VSMC migration and proliferation induced by ox-LDL. Methods: Human VSMCs (HVSMCs) were exposed to ox-LDL. Circ_0007478, microRNA (miR)-638, and rho-associated protein kinase 2 ( ROCK2) levels were gauged by quantitative real-time PCR (qRT-PCR) and western blot. Cell viability and proliferation were assessed by MTT and EdU assays, respectively. Transwell assays were used to detect cell migration and invasion. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-638 and circ_0007478 or ROCK2. Results: Our data indicated that circ_0007478 expression was augmented in AS serum samples and ox-LDL-treated HVSMCs. Depletion of circ_0007478 attenuated HVSMC proliferation, migration, and invasion induced by ox-LDL. Mechanistically, circ_0007478 targeted miR-638 by directly pairing to miR-638. Reduction of miR-638 reversed the effects of circ_0007478 depletion on ox-LDL-evoked proliferation, migration, and invasion in HVSMCs. ROCK2 was a direct miR-638 target and miR-638-mediated inhibition of ROCK2 relieved ox-LDL-evoked HVSMC proliferation, migration, and invasion. Furthermore, circ_0007478 was identified as a competing endogenous RNA (ceRNA) for miR-638 to modulate ROCK2 expression. Conclusion: Our present study establishes an undescribed ceRNA regulatory network, in which circ_0007478 targets miR-638 to upregulate ROCK2, thereby contributing to ox-LDL-induced proliferation and migration in HVSMCs.

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A Novel circUBR4/miR-491-5p/NRP2 ceRNA Network Regulates Oxidized Low-density Lipoprotein-induced Proliferation and Migration in Vascular Smooth Muscle Cells

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 6 publications

References 39 publications

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

Inhibition of ox‐LDL‐induced endothelial cell injury by LINC02381 knockdown through the microRNA‐491‐5p/transcription factor 7 axis

Regulation of oxidized LDL-induced proliferation and migration in human vascular smooth muscle cells by a novel circ_0007478/miR-638/ROCK2 ceRNA network

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