miR-155 inhibits oxidized low-density lipoprotein–induced apoptosis in different cell models by targeting the p85α/AKT pathway

Ruan, Zhimin; Chu, Tianshu; Wu, Liyong; Zhang, Mingguo; Zheng, Mei; Zhang, Qian; Zhou, Maosheng; Zhu, Guofu

doi:10.1007/s13105-020-00738-0

Cited by 10 publications

(4 citation statements)

References 34 publications

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“…There is a vast number of potential target genes regulated by miR‐15a‐5p or/and miR‐199a‐3p, which are involved in atherosclerosis, lipid metabolism and inflammation, including mTOR, 31 ET‐1, 27 YAP, 32 CXCL11, 33 CD44, 34 MAP3K4, 35 p65, 36 IKKα/β, 37 ICAM‐1 38 and p85α. 39 In addition to review of the literature, we performed in silico studies to determine possible targets of both miRNAs related to the inflammation, specifically, with proteins involved in NF‐κB pathway. We found as possible candidates: IKKα, IKKβ and p65.…”

Section: Discussionmentioning

confidence: 99%

Role of miR‐15a‐5p and miR‐199a‐3p in the inflammatory pathway regulated by NF‐κB in experimental and human atherosclerosis

González‐López,

Álvarez‐Villarreal,

Ruiz‐Simón

et al. 2023

Clinical & Translational Med

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BackgroundCardiovascular diseases (CVDs) prevalence has significantly increased in the last decade and atherosclerosis development is the main trigger. MicroRNAs (miRNAs) are non‐coding RNAs that negatively regulate gene expression of their target and their levels are frequently altered in CVDs.MethodsBy RT‐qPCR, we analysed miR‐9‐5p, miR‐15a‐5p, miR‐16‐5p and miR‐199a‐3p levels in aorta from apolipoprotein knockout (ApoE−/−) mice, an experimental model of hyperlipidemia‐induced atherosclerosis, and in human aortic and carotid atherosclerotic samples. By in silico studies, Western blot analysis and immunofluorescence studies, we detected the targets of the altered miRNAs.ResultsOur results show that miR‐15a‐5p and miR‐199a‐3p are significantly decreased in carotid and aortic samples from patients and mice with atherosclerosis. In addition, we found an increased expression in targets of both miRNAs that participate in the inflammatory pathway of nuclear factor kappa B (NF‐κB), such as IKKα, IKKβ and p65. In human vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs), the overexpression of miR‐15a‐5p or miR‐199a‐3p decreased IKKα, IKKβ and p65 protein levels as well as NF‐κB activation. On the other hand, miR‐15a‐5p and miR‐199a‐3p overexpression reduced ox‐LDL uptake and the inflammation regulated by NF‐κB in VSMCs. Moreover, although miR‐15a‐5p and miR‐199a‐3p were significantly increased in exosomes from patients with advanced carotid atherosclerosis, only in the ROC analyses for miR‐15a‐5p, the area under the curve was 0.8951 with a p value of .0028.ConclusionsOur results suggest that the decrease of miR‐199a‐3p and miR‐15a‐5p in vascular samples from human and experimental atherosclerosis could be involved in the NF‐κB activation pathway, as well as in ox‐LDL uptake by VSMCs, contributing to inflammation and progression atherosclerosis. Finally, miR‐15a‐5p could be used as a novel diagnostic biomarker for advanced atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Role of miR‐15a‐5p and miR‐199a‐3p in the inflammatory pathway regulated by NF‐κB in experimental and human atherosclerosis

González‐López,

Álvarez‐Villarreal,

Ruiz‐Simón

et al. 2023

Clinical & Translational Med

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“…Furthermore, miRNAs have become an integral part in determining the mechanisms associated with AS, and have the potential to act as biomarkers (39,40). Ruan et al (41) demonstrated that miR-155 overexpression inhibited apoptosis in different cells including vascular endothelial cells and vascular smooth muscle cells by suppressing the expression of p85α to block Akt activation, which supports a potential therapeutic role in AS. Thus, it was hypothesized that miRNA may regulate the proliferation, migration and cell viability of A7r5 cells induced by ox-LDL.…”

Section: Discussionmentioning

confidence: 99%

miR‑129‑5p inhibits oxidized low‑density lipoprotein‑induced A7r5 cell viability and migration by targeting HMGB1 and the PI3k/Akt signaling pathway

Jiang

Gong

2022

Exp Ther Med

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The mechanisms underlying gene therapy for the treatment of cardiovascular diseases remain to be elucidated. microRNAs (miRs) have been recognized as key regulators in vascular smooth muscle cells, which are involved in the formation of atherosclerosis. The present study aimed to explore the role of miR-129-5p in the regulation of high-mobility group box 1 protein (HMGB1) and the PI3k/Akt signaling pathway, and further explore the role of miR-129-5p in the viability and migration of A7r5 cells induced by oxidized low-density lipoprotein (ox-LDL). Cell viability, viability and migration were determined using Cell Counting Kit-8, colony formation, wound healing and Transwell assays. The expression levels of miR-129-5p and HMGB1 were detected using reverse transcription-quantitative PCR and western blotting. A dual-luciferase assay was used to confirm the association between miR-129-5p and HMGB1. RT-qPCR results in the present study demonstrated that the expression levels of miR-129-5p in A7r5 cells induced by ox-LDL were significantly decreased, compared with the control cells. Moreover, the viability and migration of A7r5 cells induced by ox-LDL were increased compared with control group. Western blot and RT-qPCR results showed that miR-129-5p decreased the expression of HMGB1 in A7r5 cells compared with control group. The present results demonstrated that miR-129-5p inhibited the viability, viability and migration of A7r5 cells induced by ox-LDL, and directly targeted HMGB1 to regulate the PI3k/Akt signaling pathway. In conclusion, miR-129-5p inhibited the PI3k/Akt signaling pathway by directly targeting HMGB1, and reduced the viability, viability and migration of A7r5 cells induced by ox-LDL.

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“…Atherogenesis was identified by the plaque area and plaque composition in aortic roots [ 31 ]. This is the first study to explore the effects of miRNA expression profiles in plasma extracellular vesicles of LDLr −/− mice by combining two approaches, such as high-throughput sequencing and bioinformatics analyses.…”

Section: Discussionmentioning

confidence: 99%

miRNAs from Plasma Extracellular Vesicles Are Signatory Noninvasive Prognostic Biomarkers against Atherosclerosis in LDLr-/-Mice

Zhai

Duan

Shi

et al. 2022

Oxidative Medicine and Cellular Longevity

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Circular microRNAs (miRNAs) have become central in pathophysiological conditions of atherosclerosis (AS). However, the biomarkers for diagnosis and therapeutics against AS are still unclear. The atherosclerosis models in low-density lipoprotein receptor deficiency (LDLr-/-) mice were established with a high-fat diet (HFD). The extraction kit isolated extracellular vesicles from plasma. Total RNAs were extracted from LDLr-/- mice in plasma extracellular vesicles. Significantly varying miRNAs were detected by employing Illumina HiSeq 2000 deep sequencing technology. Target gene predictions of miRNAs were employed by related software that include RNAhybrid, TargetScan, miRanda, and PITA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) further analyzed the intersection points of predicted results. The results showed that the HFD group gradually formed atherosclerotic plaques in thoracic aorta compared with the control group. Out of 17, 8 upregulated and 9 downregulated miRNAs with a significant difference were found in the plasma extracellular vesicles that were further cross-examined by sequencing and bioinformatics analysis. Focal adhesion and Ras signaling pathway were found to be the most closely related pathways through GO and KEGG pathway analyses. The 8 most differentially expressed up- and downregulated miRNAs were further ascertained by TaqMan-based qRT-PCR. TaqMan-based qRT-PCR and in situ hybridization further validated the most differentially expressed miRNAs (miR-378d, miR-181b-5p, miR-146a-5p, miR-421-3p, miR-350-3p, and miR-184-3p) that were consistent with deep sequencing analysis suggesting a promising potential of utility to serve as diagnostic biomarkers against AS. The study gives a comprehensive profile of circular miRNAs in atherosclerosis and may pave the way for identifying biomarkers and novel targets for atherosclerosis.

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miR-155 inhibits oxidized low-density lipoprotein–induced apoptosis in different cell models by targeting the p85α/AKT pathway

Cited by 10 publications

References 34 publications

Role of miR‐15a‐5p and miR‐199a‐3p in the inflammatory pathway regulated by NF‐κB in experimental and human atherosclerosis

Role of miR‐15a‐5p and miR‐199a‐3p in the inflammatory pathway regulated by NF‐κB in experimental and human atherosclerosis

miR‑129‑5p inhibits oxidized low‑density lipoprotein‑induced A7r5 cell viability and migration by targeting HMGB1 and the PI3k/Akt signaling pathway

miRNAs from Plasma Extracellular Vesicles Are Signatory Noninvasive Prognostic Biomarkers against Atherosclerosis in LDLr-/-Mice

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