The Yin and Yang of epigenetics in the field of nanoparticles

Musolino, Elettra; Pagiatakis, Christina; Serio, Simone; Borgese, Marina; Gamberoni, Federica; Gornati, Rosalba; Bernardini, Giovanni; Papait, Roberto

doi:10.1039/d1na00682g

Cited by 18 publications

(13 citation statements)

References 132 publications

(237 reference statements)

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“…Previous studies related to the AgNPs mediated epigenetic toxicity mainly focuses on DNA and histone modifications, or alterations of miRNA expression. 34–37 In this unique research, we have shown that GO-AgNPs cause differential expression of circRNAs and lncRNAs in RFFCs. In addition, we have constructed a comprehensive network map of circRNA–miRNA–mRNA that shows the potential scenario of how circRNAs are regulating gene expression by interacting with the miRNAs.…”

Section: Discussionmentioning

confidence: 86%

Multiple RNA Profiling Reveal Epigenetic Toxicity Effects of Oxidative Stress by Graphene Oxide Silver Nanoparticles in-vitro

Yuan¹,

Zhang²,

Liu³

et al. 2023

IJN

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Introduction The increasing industrial and biomedical utilization of graphene oxide silver nanoparticles (GO-AgNPs) raises the concern of nanosafety: exposure to the AgNPs or GO-AgNPs increases the generation of reactive oxygen species (ROS), causes DNA damage and alters the expression of whole transcriptome including mRNA, miRNA, tRNA, lncRNA, circRNA and others. Although the roles of different RNAs in epigenetic toxicity are being studied during the last decade, but still we have little knowledge about the role of circle RNAs (circRNAs) in epigenetic toxicity. Methods Rabbit fetal fibroblast cells (RFFCs) were treated with 0, 8, 16, 24, 32 and 48 μg/mL GO-AgNPs to test the cell viability and 24 μg/mL GO-AgNPs was selected as the experimental dose. After 24 h treatment with 24 μg/mL GO-AgNPs, the level of ROS, malondialdehyde (MDA), superoxide dismutase (SOD), intracellular ATP, glutathione peroxidase (GPx), and glutathione reductase (Gr) were measured in the RFFCs. High-throughput whole transcriptome sequencing was performed to compare the expression of circRNAs, long non-coding RNAs (lncRNA) and mRNA between 24 μg/mL GO-AgNPs-treated RFFCs and control cells. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to validate the accuracy of circRNA sequencing data. Bioinformatics analyses were performed to reveal the potential functional roles and related pathways of differentially expressed circRNAs, lncRNA and mRNA and to construct a circRNA–miRNA–mRNA interaction network. Results We found that 57 circRNAs, 75 lncRNAs, and 444 mRNAs were upregulated while 35 circRNAs, 21 lncRNAs, and 186 mRNAs were downregulated. These differentially expressed genes are mainly involved in the transcriptional mis-regulation of cancer through several pathways: MAPK signaling pathway (circRNAs), non-homologous end-joining (lncRNAs), as well as PPAR and TGF-beta signaling pathways (mRNAs). Conclusion These data revealed the potential roles of circRNAs in the GO-AgNPs induced toxicity through oxidative damage, which would be the basis for further research to determine their roles in the regulation of different biological processes.

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Section: Discussionmentioning

confidence: 86%

Multiple RNA Profiling Reveal Epigenetic Toxicity Effects of Oxidative Stress by Graphene Oxide Silver Nanoparticles in-vitro

Yuan¹,

Zhang²,

Liu³

et al. 2023

IJN

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“…Therefore, current studies have proposed that ncRNAs combined with biocompatible nanoparticles (NPs) can offer better therapeutic properties. Using NPs as delivery vectors can reduce drug toxicity, facilitate targeted drug release, and increase drug bioavailability, which provides an optimized therapeutic strategy for the cardiovascular field ( 125 , 128 – 130 ). In addition, with the production of proteasome inhibitors, the UPS offers a new therapeutic frontier.…”

Section: Prognostic and Therapeutic Targetsmentioning

confidence: 99%

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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“…In light of this, ncRNAs are increasingly proposed for therapeutic applications in association with biocompatible nanoparticles (NPs). These are small particles with a diameter ranging from 1 to 100 nm, already effectively used for the transport and release of antibiotics, anticancer drugs, and for viral or non-viral genes to the site of interest without being recognized by the immune system [84].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Non-Coding RNAs in Cell-to-Cell Communication: Exploiting Physiological Mechanisms as Therapeutic Targets in Cardiovascular Pathologies

Francés

Musolino

Papait

et al. 2023

IJMS

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Cardiovascular disease, the leading cause of death worldwide, has been characterized at the molecular level by alterations in gene expression that contribute to the etiology of the disease. Such alterations have been shown to play a critical role in the development of atherosclerosis, cardiac remodeling, and age-related heart failure. Although much is now known about the cellular and molecular mechanisms in this context, the role of epigenetics in the onset of cardiovascular disease remains unclear. Epigenetics, a complex network of mechanisms that regulate gene expression independently of changes to the DNA sequence, has been highly implicated in the loss of homeostasis and the aberrant activation of a myriad of cellular pathways. More specifically, non-coding RNAs have been gaining much attention as epigenetic regulators of various pathologies. In this review, we will provide an overview of the ncRNAs involved in cell-to-cell communication in cardiovascular disease, namely atherosclerosis, cardiac remodeling, and cardiac ageing, and the potential use of epigenetic drugs as novel therapeutic targets.

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The Yin and Yang of epigenetics in the field of nanoparticles

Abstract: Nanoparticles (NPs) have become a very exciting research avenue, with multitudinous applications in various fields, including the biomedical one, whereby they have been gaining considerable interest as drug carriers able...

Cited by 18 publications

References 132 publications

Multiple RNA Profiling Reveal Epigenetic Toxicity Effects of Oxidative Stress by Graphene Oxide Silver Nanoparticles in-vitro

Multiple RNA Profiling Reveal Epigenetic Toxicity Effects of Oxidative Stress by Graphene Oxide Silver Nanoparticles in-vitro

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

Non-Coding RNAs in Cell-to-Cell Communication: Exploiting Physiological Mechanisms as Therapeutic Targets in Cardiovascular Pathologies

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