Expression of <scp>miRNAs</scp> in plasma exosomes derived from patients with atrial fibrillation

Zhang, Wei; Zhang, Bing; Shaohuan, Qian; Wang, Yanran; Sun, Shuhong; Tang, Bi; Zhu, Feiqi; Zhang, Heng; Gao, Qin; Kang, Pan

doi:10.1002/clc.23461

Cited by 25 publications

(19 citation statements)

References 36 publications

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“…Let-7b-3p, previously known as let-7b, was conventionally regarded as the passenger strand was considered to have no biological function. In recent years, however, relevant studies have revealed let-7b-3p to play a significant role in various of diseases (13)(14)(15). Despite this, the specific role and mechanism of let-7b-3p in LUAD remains unclear.…”

Section: Original Articlementioning

confidence: 99%

Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma

Li¹,

Dong²,

Lü³

et al. 2021

Transl Lung Cancer Res

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Background: Lung cancer is a malignant tumor with the highest morbidity and mortality rates worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Overall, current treatments of LUAD are not satisfactory; therefore, novel targets need to be explored. Let-7b-3p is an important member of the let-7 family of microRNAs (miRNAs), and has not been studied separately in LUAD. This study aimed to investigate the role and molecular mechanism of let-7b-3p in LUAD.Methods: Herein, let-7b-3p expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) assays. MTT, colony formation assay, flow cytometry analysis, wound-healing, Transwell and in vivo experiments were conducted to assess let-7b-3p's function in LUAD. The downstream target TFIIB-related factor 2 (BRF2) was predicted using bioinformatics analyses and confirmed by dual-luciferase reporter assay and rescue experiments. Additionally, BRF2 was found to affect the MAPK/ERK pathway through transcriptome sequencing analysis and western blot (WB) assay.Results: Let-7b-3p is downregulated in LUAD cells and tissue samples and low let-7b-3p expression is correlated with a poor prognosis in LUAD patients. Let-7b-3p suppresses the proliferation and metastasis of LUAD cells both in vivo and in vitro by directly targeting the BRF2-mediated MAPK/ERK pathway.Conclusions: Let-7b-3p inhibits the development of LUAD and is an ideal novel therapeutic target for the treatment of LUAD.

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Section: Original Articlementioning

confidence: 99%

Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma

Li¹,

Dong²,

Lü³

et al. 2021

Transl Lung Cancer Res

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“…To date, evidence regarding associations between exosomes and AF has mainly focused on clinical research. Some scholars found that plasma exosomes differentially expressed miRNAs between AF and sinus rhythm (9,10). Bioinformatics analysis showed that these miRNAs and their targets possibly contribute to atrial fibrosis (11).…”

Section: Introductionmentioning

confidence: 99%

Blockade of Exosome Release Suppresses Atrial Fibrillation by Alleviating Atrial Fibrosis in Canines With Prolonged Atrial Pacing

Yao

Wang

et al. 2021

Front. Cardiovasc. Med.

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Background: Clinical studies have shown that exosomes are associated with atrial fibrillation (AF). However, the roles and underlying mechanisms remain unclear. Hence, this study aimed to investigate the function of exosomes in AF development.Methods: Twenty beagles were randomly divided into the sham group (n = 6), the pacing group (n = 7), and the pacing + GW4869 group (n = 7). The pacing and GW4869 groups underwent rapid atrial pacing (450 beats/min) for 7 days. The GW4869 group received intravenous GW4869 injection (an inhibitor of exosome biogenesis/release, 0.3 mg/kg, once a day) during pacing. Electrophysiological measurements, transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT-PCR, Masson's staining, and immunohistochemistry were performed in this study.Results: Rapid atrial pacing increased the release of plasma and atrial exosomes. GW4869 treatment markedly suppressed AF inducibility and reduced the release of exosomes. After 7 days of pacing, the expression of transforming growth factor-β1 (TGF-β1), collagen I/III, and matrix metalloproteinases was enhanced in the atrium, and the levels of microRNA-21-5p (miR-21-5p) were upregulated in both plasma exosomes and the atrium, while the tissue inhibitor of metalloproteinase 3 (TIMP3), a target of miR-21-5p, showed a lower expression in the atrium. The administration of GW4869 abolished these effects.Conclusions: The blockade of exosome release with GW4869 suppressed AF by alleviating atrial fibrosis in a canine model, which was probably related to profibrotic miR-21-5p enriched in exosomes and its downstream TIMP3/TGF-β1 pathway.

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“…Furthermore, virtually every stage of cancer progression starting from early signs of transformation to metastasis influences the miRNA profile of exosomes (reviewed in [24]. Owing to sensitivity of changing environment, exosome miRNA signatures have been shown to be biomarkers for various metabolic conditions like atrial fibrillation [25], renal graft function [26], pancreatic lesions [27], liver disease [28] and various types of cancers as reviewed in [29]. In addition to a prognostic tool, miRNAs have been shown to influence both local and distal gene regulation when packaged and delivered to cells via exosomes.…”

Section: Mirnamentioning

confidence: 99%

The Multifunctionality of Exosomes; from the Garbage Bin of the Cell to a Next Generation Gene and Cellular Therapy

Shrivastava

Morris

2021

Genes

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Exosomes are packaged with a variety of cellular cargo including RNA, DNA, lipids and proteins. For several decades now there has been ongoing debate as to what extent exosomes are the garbage bin of the cell or if these entities function as a distributer of cellular cargo which acts in a meaningful mechanistic way on target cells. Are the contents of exosomes unwanted excess cellular produce or are they selective nucleic acid packaged nanoparticles used to communicate in a paracrine fashion? Overexpressed RNAs and fragments of DNA have been shown to collect into exosomes which are jettisoned from cells in response to particular stimuli to maintain homeostasis suggesting exosomes are functional trash bins of the cell. Other studies however have deciphered selective packaging of particular nucleic acids into exosomes. Nucleic acids packaged into exosomes are increasingly reported to exert transcriptional control on recipient cells, supporting the notion that exosomes may provide a role in signaling and intracellular communication. We survey the literature and conclude that exosomes are multifunctional entities, with a plethora of roles that can each be taken advantage to functionally modulate cells. We also note that the potential utility of developing exosomes as a next generation genetic therapy may in future transform cellular therapies. We also depict three models of methodologies which can be adopted by researchers intending to package nucleic acid in exosomes for developing gene and cell therapy.

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Expression of miRNAs in plasma exosomes derived from patients with atrial fibrillation

Cited by 25 publications

References 36 publications

Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma

Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma

Blockade of Exosome Release Suppresses Atrial Fibrillation by Alleviating Atrial Fibrosis in Canines With Prolonged Atrial Pacing

The Multifunctionality of Exosomes; from the Garbage Bin of the Cell to a Next Generation Gene and Cellular Therapy

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