<scp>LncRNA MEG3</scp>ameliorates<scp>NiO</scp>nanoparticles‐induced pulmonary inflammatory damage via suppressing the p38 mitogen activated protein kinases pathway

Chang, Xuhong; Gao, Qing; Gong, Xuefeng; Zheng, Jiyue; Liu, Han; Li, Kun; Zhan, Haibing; Wang, Xiaoxia; Sheng, Li; Sun, Xingchang; Feng, San-wei; Sun, Yuhao

doi:10.1002/tox.23464

Cited by 9 publications

(9 citation statements)

References 54 publications

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“…Based on our previous studies, a rat pulmonary fibrosis model was successfully established using the same methodology 22,23 . Our results of pathological damage to lung tissue in rats have been published in a previous study 34 …”

Section: Resultsmentioning

confidence: 99%

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A transcriptomics‐based investigation of the mechanism of pulmonary fibrosis induced by nickel oxide nanoparticles

Liu,

Yang,

et al. 2024

Environmental Toxicology

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Nickel oxide nanoparticles (NiONPs) are an emerging nanomaterial, which poses a huge threat to the health of workplace population. Nanoparticles induce pulmonary fibrosis, and its mechanisms are associated with noncoding RNAs (ncRNAs). However, ncRNAs and competing endogenous RNA (ceRNA) networks which involved in NiONP‐induced pulmonary fibrosis are still unclear. This study aimed to identify ncRNA‐related ceRNA networks and investigate the role of the Wnt/β‐catenin pathway in pulmonary fibrosis. Male Wistar rats were intratracheally instilled with 0.015, 0.06, and 0.24 mg/kg NiONPs twice a week for 9 weeks. First, we found there were 93 circularRNAs (circRNAs), 74 microRNAs (miRNAs), 124 long non‐coding RNAs (lncRNAs), and 1675 messenger RNAs (mRNAs) differentially expressed through microarray analysis. Second, we constructed ceRNA networks among lncRNAs/circRNAs, miRNAs and mRNAs and identified two ceRNA networks (lncMelttl16/miR‐382‐5p/Hsd17b7 and circIqch/miR‐181d‐5p/Stat1) after real time‐quantitative polymerase chain reaction (RT–qPCR) validation. Furthermore, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, ncRNAs were found to be involved in biological processes and signaling pathways related to pulmonary fibrosis. KEGG analysis showed that NiONPs activated the Wnt/β‐catenin pathway in rats. In vitro, HFL1 cells were treated with 0, 50, 100, and 200 μg/mL NiONPs for 24 h. We found that NiONPs induced collagen deposition and Wnt/β‐catenin pathway activation. Moreover, a blockade of Wnt/β‐catenin pathway alleviated NiONP‐induced collagen deposition. In conclusion, these observations suggested that ncRNAs were crucial in pulmonary fibrosis development and that the Wnt/β‐catenin pathway mediated the deposition of collagen.

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Section: Resultsmentioning

confidence: 99%

“…22,23 Our results of pathological damage to lung tissue in rats have been published in a previous study. 34…”

Section: Establishment Of the Nionp-induced Pulmonary Fibrosis Rat Modelmentioning

confidence: 99%

A transcriptomics‐based investigation of the mechanism of pulmonary fibrosis induced by nickel oxide nanoparticles

Liu,

Yang,

et al. 2024

Environmental Toxicology

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“… 61 Yang et al confirmed nickel oxide nanoparticle exposure downregulated MEG3 in A549 cells and lung tissues; overexpression of MEG3 significantly suppressed nanoparticle-induced inflammatory cytokines (IL1β, IL6, TNF-α, CXCL1 and CXCL2). 62 In this study, we screened two crucial lncRNAs SCAT8 and LUCAT1 in MWCNT-exposed ARPE-19 cells. Both of them regulated the expression of all FOS-mediated pro-inflammatory pathway genes ( CXCL8, MMP1, CASP3, FOS, CXCL2 and IL11 ).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells

Luo¹,

Xie²,

Su³

et al. 2023

IJN

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Background The wide application of multi-walled carbon nanotubes (MWCNTs) in various fields has raised enormous concerns regarding their safety for humans. However, studies on the toxicity of MWCNTs to the eye are rare and potential molecular mechanisms are completely lacking. This study was to evaluate the adverse effects and toxic mechanisms of MWCNTs on human ocular cells. Methods Human retinal pigment epithelial cells (ARPE-19) were treated with pristine MWCNTs (7–11 nm) (0, 25, 50, 100 or 200 μg/mL) for 24 hours. MWCNTs uptake into ARPE-19 cells was examined using transmission electron microscopy (TEM). The cytotoxicity was evaluated by CCK-8 assay. The death cells were detected by Annexin V-FITC/PI assay. RNA profiles in MWCNT-exposed and non-exposed cells (n = 3) were analyzed using RNA-sequencing. The differentially expressed genes (DEGs) were identified through the DESeq2 method and hub of which were filtered by weighted gene co-expression, protein–protein interaction (PPI) and lncRNA-mRNA co-expression network analyses. The mRNA and protein expression levels of crucial genes were verified using quantitative polymerase chain reaction (qPCR), colorimetric analysis, ELISA and Western blotting. The toxicity and mechanisms of MWCNTs were also validated in human corneal epithelial cells (HCE-T). Results TEM analysis indicated the internalization of MWCNTs into ARPE-19 cells to cause cell damage. Compared with untreated ARPE-19 cells, those exposed to MWCNTs exhibited significantly decreased cell viabilities in a dose-dependent manner. The percentages of apoptotic (early, Annexin V positive; late, Annexin V and PI positive) and necrotic (PI positive) cells were significantly increased after exposure to IC50 concentration (100 μg/mL). A total of 703 genes were identified as DEGs; 254 and 56 of them were, respectively, included in darkorange2 and brown1 modules that were significantly associated with MWCNT exposure. Inflammation-related genes (including CXCL8, MMP1, CASP3, FOS, CXCL2 and IL11 ) were screened as hub genes by calculating the topological characteristics of genes in the PPI network. Two dysregulated long non-coding RNAs ( LUCAT1 and SCAT8 ) were shown to regulate these inflammation-related genes in the co-expression network. The mRNA levels of all eight genes were confirmed to be upregulated, while caspase-3 activity and the release of CXCL8, MMP1, CXCL2, IL11 and FOS proteins were demonstrated to be increased in MWCNT-treated ARPE-19 cells. MWCNTs exposure also can induce cytotoxicity and increase the caspase-3 activity and the expression of LUCAT1, MMP1, CXCL2, and IL11 mRNA and protein in HCE-T cells. Conclusion Our study provides promising biomarkers for monitoring MWCNT-induced eye disorders and targets for developing preventive and therapeutic strategies.

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“…The overexpression of MEG3 inhibited the Hedgehog pathway activated by NiO NPs exposure [ 97 ]. While the exposure of NiO NPs to rats activated the p38 MAPK and induced inflammatory responses, the overexpression of MEG3 suppressed the p38 MAPK, resulting in reduced levels of inflammatory cytokines, including IL-6, IL-8, and TNF-α [ 98 ].…”

Section: Meg3 In Carcinogenesis Of Heavy Metalsmentioning

confidence: 99%

Long Non-Coding RNA MEG3 in Metal Carcinogenesis

Zhang

Shi

et al. 2023

Toxics

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Most transcripts from human genomes are non-coding RNAs (ncRNAs) that are not translated into proteins. ncRNAs are divided into long (lncRNAs) and small non-coding RNAs (sncRNAs). LncRNAs regulate their target genes both transcriptionally and post-transcriptionally through interactions with proteins, RNAs, and DNAs. Maternally expressed gene 3 (MEG3), a lncRNA, functions as a tumor suppressor. MEG3 regulates cell proliferation, cell cycle, apoptosis, hypoxia, autophagy, and many other processes involved in tumor development. MEG3 is downregulated in various cancer cell lines and primary human cancers. Heavy metals, such as hexavalent chromium (Cr(VI)), arsenic, nickel, and cadmium, are confirmed human carcinogens. The exposure of cells to these metals causes a variety of cancers. Among them, lung cancer is the one that can be induced by exposure to all of these metals. In vitro studies have demonstrated that the chronic exposure of normal human bronchial epithelial cells (BEAS-2B) to these metals can cause malignant cell transformation. Metal-transformed cells have the capability to cause an increase in cell proliferation, resistance to apoptosis, elevated migration and invasion, and properties of cancer stem-like cells. Studies have revealed that MEG is downregulated in Cr(VI)-transformed cells, nickel-transformed cells, and cadmium (Cd)-transformed cells. The forced expression of MEG3 reduces the migration and invasion of Cr(VI)-transformed cells through the downregulation of the neuronal precursor of developmentally downregulated protein 9 (NEDD9). MEG3 suppresses the malignant cell transformation of nickel-transformed cells. The overexpression of MEG3 decreases Bcl-xL, causing reduced apoptosis resistance in Cd-transformed cells. This paper reviews the current knowledge of lncRNA MEG3 in metal carcinogenesis.

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LncRNA MEG3amelioratesNiOnanoparticles‐induced pulmonary inflammatory damage via suppressing the p38 mitogen activated protein kinases pathway

Cited by 9 publications

References 54 publications

A transcriptomics‐based investigation of the mechanism of pulmonary fibrosis induced by nickel oxide nanoparticles

A transcriptomics‐based investigation of the mechanism of pulmonary fibrosis induced by nickel oxide nanoparticles

Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells

Long Non-Coding RNA MEG3 in Metal Carcinogenesis

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