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PM2.5 induces the distant metastasis of lung adenocarcinoma via promoting the stem cell properties of cancer cells Texte intégral
2022
Pan, Junyi | Xue, Yueguang | Li, Shilin | Wang, Liuxiang | Mei, Jie | Ni, Dongqi | Jiang, Jipeng | Zhang, Meng | Yi, Shaoqiong | Zhang, Rong | Ma, Yongfu | Liu, Yang | Liu, Ying
Lung cancer is the most common cancer in China and second worldwide, of which the incidence of lung adenocarcinoma is rising. As an independent factor, air pollution has drawn the attention of the public. An increasing body of studies has focused on the effect of PM₂.₅ on lung adenocarcinoma; however, the mechanism remains unclear. We collected the PM₂.₅ in two megacities, Beijing (BPM) and Shijiazhuang (SPM), located in the capital of China, and compared the different components and sources of PM₂.₅ in the two cities. Vehicle emissions are the primary sources of BPM, whereas SPM is industrial emissions. We found that chronic exposure to PM₂.₅ promotes the tumorigenesis and metastasis of lung adenocarcinoma in patient-derived xenograft (PDX) models, as well as the migration and invasion of lung adenocarcinoma cell lines. SPM has more severe effects in vivo and in vitro. The underlying mechanisms are related to the stem cell properties of cancer cells, the epithelial-mesenchymal transition (EMT) process, and the corresponding miRNAs. It is hopeful to provide a theoretical basis for improving air pollution in China, especially in the capital area, and is of the significance of long-term survival of lung cancer patients.
Afficher plus [+] Moins [-]Association between fine particulate matter and coronary heart disease: A miRNA microarray analysis Texte intégral
2022
Guo, Jianhui | Xie, Xiaoxu | Wu, Jieyu | Yang, Le | Ruan, Qishuang | Xu, Xingyan | Wei, Donghong | Wen, Yeying | Wang, Tinggui | Hu, Yuduan | Lin, Yawen | Chen, Mingjun | Wu, Jiadong | Lin, Shaowei | Li, Huangyuan | Wu, Siying
Several studies have reported an association between residential surrounding particulate matter with an aerodynamic diameter ≤2.5 μm (PM₂.₅) and coronary heart disease (CHD). However, the underlying biological mechanism remains unclear. To fill this research gap, this study enrolled a residentially stable sample of 942 patients with CHD and 1723 controls. PM₂.₅ concentration was obtained from satellite-based annual global PM₂.₅ estimates for the period 1998–2019. MicroRNA microarray and pathway analysis of target genes was performed to elucidate the potential biological mechanism by which PM₂.₅ increases CHD risk. The results showed that individuals exposed to high PM₂.₅ concentrations had higher risks of CHD than those exposed to low PM₂.₅ concentrations (odds ratio = 1.22, 95% confidence interval: 1.00, 1.47 per 10 μg/m³ increase in PM₂.₅). Systolic blood pressure mediated 6.6% of the association between PM₂.₅ and CHD. PM₂.₅ and miR-4726-5p had an interaction effect on CHD development. Bioinformatic analysis demonstrated that miR-4726-5p may affect the occurrence of CHD by regulating the function of RhoA. Therefore, individuals in areas with high PM₂.₅ exposure and relative miR-4726-5p expression have a higher risk of CHD than their counterparts because of the interaction effect of PM₂.₅ and miR-4726-5p on blood pressure.
Afficher plus [+] Moins [-]Short-term ambient particulate air pollution exposure, microRNAs, blood pressure and lung function Texte intégral
2022
Cong, Xiaowei | Zhang, Juan | Sun, Rongli | Pu, Yuepu
Ambient particulate air pollution is a risk factor for cardiovascular and respiratory disease, yet the biological mechanisms underlying this association are not well understood. The current study aimed to investigate the mediation role of microRNAs on the association between personal PM₂.₅ exposure and blood pressure and lung function. One hundred and twenty adults (60 truck drivers and 60 office workers) aged 18–46 years were assessed on the June 15, 2008 and at follow-up (1- to 2-weeks later). MicroRNAs were extracted from the peripheral blood samples. Compared to truck drivers, there is a significant increase in FEF₂₅₋₇₅, FEV₁, and FEV₁/FVC and a decrease in PM₂.₅ in office workers (all p < 0.05). According to the Bonferroni corrected threshold p-value < 6.81 × 10⁻⁵ (0.05/734) used, personal PM₂.₅ data showed a significant positive association with miR-644 after the adjustment for age, BMI, smoking status, and habitual alcohol use. The mediation effect of miR-644 on the association between personal PM₂.₅ exposure and FEF₂₅₋₇₅ [B (95%CI) = −1.342 (−2.810, −0.113)], PEF [B (95%CI) = -1.793 (−3.926, −0.195)], and FEV₁/FVC [B (95%CI) = −0.119‰ (−0.224‰, −0.026‰)] was significant only for truck drivers after the adjustment for covariates. There were no similar associations with blood pressure. These results demonstrate microRNAs to potentially mediate association of PM₂.₅ with lung function. Subsequent studies are needed to further elucidate the potential mechanisms of action by which the mediation effect of microRNAs is achieved with this process.
Afficher plus [+] Moins [-]The contributions of miR-25-3p, oxidative stress, and heat shock protein in a complex mechanism of autophagy caused by pollutant cadmium in common carp (Cyprinus carpio L.) hepatopancreas Texte intégral
2021
Li, Zhuo | Ali Shah, Syed Waqas | Zhou, Qin | Yin, Xiujie | Teng, Xiaohua
Cadmium (Cd) is a toxic heavy metal that can be discharged into water environment through industrial activities, threatening the health of aquatic organisms and humans. MicroRNA (miRNA) plays an important role in the process of autophagy. The purpose of this experiment was to study the mechanism of Cd-induced autophagy in common carp hepatopancreas. We established a Cd poisoning model of common carp and explored ultrastructure, two oxidation indicators, three antioxidant indicators, miR-25-3p, two heat shock proteins (Hsps), and nine autophagy-related genes. The results confirmed that deleterious effect of Cd caused the injury of hepatopancreas and the appearance of hepatopancreas autophagic cells in common carp. At the same time, Cd exposure increased the contents of hydrogen peroxide (H₂O₂) and malonaldehyde (MDA), and decreased the activities of catalase (CAT), superoxide dismutase (SOD), and total antioxidative capacity (T-AOC), meaning that Cd caused oxidative stress via the imbalance between peroxide level and antioxidant capacity. Moreover, exposure to Cd increased mRNA expression of microtubule associated protein-1 light chain 3 beta (LC3-II), Dynein, Beclin 1, autophagy-related gene 5 (Atg5), and autophagy-related gene 12 (Atg12); and decreased mRNA expression of mechanistic target of rapamycin kinase (mTOR), indicating that excess Cd caused autophagy, and AMPK/mTOR/ULK1 signaling pathway took part in autophagy induced by Cd in common carp hepatopancreas. Furthermore, Cd down-regulated miR-25-3p and up-regulated its three target genes (AMPK, ULK1 as well as PTEN), suggesting that miR-25-3p mediated autophagy induced by Cd. In addition, we found that Hsps were activated via the up-regulation of Hsp70 and Hsp90. Moreover, oxidative stress mediated autophagy via Hsps in Cd-treated common carp hepatopancreas and Cd-induced autophagy was time dependent. In summary, miR-25-3p, oxidative stress, and Hsps participated in autophagy caused by Cd in common carp hepatopancreas. This study provided a new idea for the mechanism of Cd-induced autophagy in hepatopancreas.
Afficher plus [+] Moins [-]Transcriptome analysis reveals that hydrogen sulfide exposure suppresses cell proliferation and induces apoptosis through ciR-PTPN23/miR-15a/E2F3 signaling in broiler thymus Texte intégral
2021
Xueyuan, Hu | Qianru, Chi | Zhaoyi, Liu | Dayong, Tao | Yu, Wang | Yimei, Cong | Shu, Li
The immune organs, like thymus, are one of the targets of hydrogen sulfide (H₂S). Previously we reported that H₂S induced the differential expression of mRNAs that implicating apoptosis in thymus, however, the roles of noncoding RNAs (ncRNAs) in H₂S-induced thymus injury are still unknown. Pollution gases could alter the expression of ncRNAs, which have been shown to play important roles in many physiological and pathophysiological processes, including immune activity. This study revealed that H₂S exposure induced 9 differentially expressed circRNAs and 15 differentially expressed miRNAs in chicken thymus. Furthermore, the circRNA - miRNA - mRNA network was constructed. We discovered that circR-PTPN23 - miR-15a - E2F3 was involved in the cell cycle and apoptosis. Further, an in vitro H₂S exposure model was established using HD11 cell line and demonstrated that H₂S suppressed cell proliferation and induced apoptosis. Moreover, ciR-PTPN23 and E2F3 were downregulated, but miR-15a was upregulated in both the thymus and HD11 cell line after H₂S exposure. Bioinformatics analysis revealed that ciR-PTPN23 directly bound to miR-15a and that E2F3 was the target gene of miR-15a. Knocking down ciR-PTPN23 suppressed HD11 proliferation and caused G1 arrest and apoptosis, however, this phenomenon could be partially reversed by ciR-PTPN23 overexpression or miR-15a silencing. In summary, the ciR-PTPN23 - miR-15a - E2F3 axis was involved in H₂S-induced cell proliferation suppression and apoptosis.
Afficher plus [+] Moins [-]microRNAs expression in relation to particulate matter exposure: A systematic review Texte intégral
2020
MicroRNAs (miRNAs) are a class of small, non-coding RNAs with a post-transcriptional regulatory function on gene expression and cell processes, including proliferation, apoptosis and differentiation. In recent decades, miRNAs have attracted increasing interest to explore the role of epigenetics in response to air pollution. Air pollution, which always contains kinds of particulate matters, are able to reach respiratory tract and blood circulation and then causing epigenetics changes. In addition, extensive studies have illustrated that miRNAs serve as a bridge between particulate matter exposure and health-related effects, like inflammatory cytokines, blood pressure, vascular condition and lung function. The purpose of this review is to summarize the present knowledge about the expression of miRNAs in response to particulate matter exposure. Epidemiological and experimental studies were reviewed in two parts according to the size and source of particles. In this review, we also discussed various functions of the altered miRNAs and predicted potential biological mechanism participated in particulate matter-induced health effects. More rigorous studies are worth conducting to understand contribution of particulate matter on miRNAs alteration and the etiology between environmental exposure and disease development.
Afficher plus [+] Moins [-]miRNAs deregulation in serum of mice is associated with lung cancer related pathway deregulation induced by PM2.5 Texte intégral
2019
Ning, Jie | Li, Peiyuan | Zhang, Boyuan | Han, Bin | Su, Xuan | Wang, Qian | Wang, Xiurong | Li, Binghua | Kang, Hui | Zhou, Lixiao | Chu, Chen | Zhang, Ning | Pang, Yaxian | Niu, Yujie | Zhang, Rong
Ambient fine particulate matter (PM2.5) as an environmental pollution has been associated with the lung cancer. However, the mechanism of epigenetics such as miRNAs deregulation between PM2.5-exposure and lung cancer has not been elucidated clearly. Twenty C57BL/6 mice were divided randomly into 2 groups and exposed to the filtered air (FA) and the concentrated air (CA), respectively. The FA mice were exposed to filtered air in chambers with a high-efficient particulate air filter (HEPA-filter), and the CA mice were exposed to concentration ambient PM2.5. The total duration of exposure was performed 6 h per day from December 1st, 2017 to January 27th, 2018. The mice exposed 900.21 μg/m³ PM2.5 for 6 h per day in CA chamber, which was nearly equaled to 225.05 μg/m³ for 24-h calculatingly. After exposure, the serum miRNAs levels were detected by microarray. Genetic and pathological alterations in lung of mice with/without PM2.5 exposure were detected. 38 differential miRNAs in serum of mice were found after PM2.5 exposure for 8 weeks. Among of them, 13 miRNAs related with lung cancer were consistent in serum and lung of mice. The target genes of 13 deregulated miRNAs including CRK, NR2F2, VIM, RASSF1, CCND2, PRKCA, SIRT1, CDK6, MAP3K7, HIF1A, UBE2V2, ATG10, BAX, E2F1, RASSF5 and CTNNB1, could involve in the pathway of lung cancer developing. Compared with the FA group, the significantly increases of histopathological changes, ROS and DNA damage were observed in lung of mice in CA group. Our study suggested that miRNAs in serum could be identified as candidate biomarkers to predict the lung cancer development during early PM2.5 exposure.
Afficher plus [+] Moins [-]Double-edged effects of noncoding RNAs in responses to environmental genotoxic insults: Perspectives with regards to molecule-ecology network Texte intégral
2019
Huang, Ruixue | Zhou, PingKun
Numerous recent studies have underlined the crucial players of noncoding RNAs (ncRNAs), i.e., microRNAs(miRNAs), long noncoding RNAs(lncRNAs) and circle RNAs(circRNAs) participating in genotoxic responses induced by a wide variety of environmental genotoxicants consistently. Genotoxic-derived ncRNAs provide us a new epigenetic molecular–ecological network (MEN) insights into the underlying mechanisms regarding genotoxicant exposure and genotoxic effects, which can modify ncRNAs to render them “genotoxic” and inheritable, thus potentially leading to disease risk via epigenetic changes. In fact, the spatial structures of ncRNAs, particularly of secondary and three-dimensional structures, diverse environmental genotoxicants as well as RNA splicing and editing forma dynamic pool of ncRNAs, which constructs a MEN in cells together with their enormous targets and interactions, making biological functions more complicated. We nonetheless suggest that ncRNAs have both beneficial(positive) and harmful(negative) effects, i.e., are “double-edged” in regulating genotoxicant toxic responses. Understanding the “double-edged” effects of ncRNAs is of crucial importance for our further comprehension of the pathogenesis of human diseases induced by environmental toxicants and for the construction of novel prevention and therapy targets. Furthermore, the MEN formed by ncRNAs and their interactions each other as well as downstream targets in the cells is important for considering the active relationships between external agents (environmental toxicants) and inherent genomic ncRNAs, in terms of suppression or promotion (down- or upregulation), and engineered ncRNA therapies can suppress or promote the expression of inherent genomic ncRNAs that are targets of environmental toxicants. Moreover, the MEN would be expected to be would be applied to the mechanistic explanation and risk assessment at whole scene level in environmental genotoxicant exposure. As molecular biology evolves rapidly, the proposed MEN perspective will provide a clearer or more comprehensive holistic view.
Afficher plus [+] Moins [-]MicroRNA-26a-CD36 signaling pathway: Pivotal role in lipid accumulation in hepatocytes induced by PM2.5 liposoluble extracts Texte intégral
2019
Ding, Dongxiao | Ye, Guozhu | Lin, Yi | Lu, Yanyang | Zhang, Han | Zhang, Xu | Hong, Zhenyu | Huang, Qiansheng | Chi, Yulang | Chen, Jinsheng | Dong, Sijun
Exposure to ambient particular matters (PM) has been associated with the development of non-alcoholic fatty liver disease (NAFLD), but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study aimed to explore the role of miRNA-mRNA regulation underlying abnormal lipid metabolism triggered by PM₂.₅liposoluble extracts. We confirmed that 72-h exposure to liposoluble extracts of PM₂.₅ from Nanjing at 25 μg/cm² induced lipid accumulation in HepG2 cells by promoting uptake of free fatty acids (FFAs). Notably, lipid accumulation induced by PM₂.₅ liposoluble extracts was associated with decreased expression of miR-26a and consequent upregulation of fatty acid translocase (FAT, also known as CD36). Using gain- and loss-of-function assays, we demonstrated that miR-26a negatively regulated CD36 to mediate lipid accumulation in HepG2 cells. We further confirmed that miR-26a directly acted on the 3′ untranslated region (3′UTR) of CD36. Furthermore, overexpression of miR-26a abolished steatosis in HepG2 cells treated with PM₂.₅ liposoluble extracts by suppressing CD36. In addition, we demonstrated that PM₂.₅ liposoluble extracts caused inflammation in HepG2 cells by raising p65 phosphorylation, thereby fuelling the transition from simple non-alcoholic fatty liver to non-alcoholic steatohepatitis. In conclusion, this study demonstrated a novel mechanism by which miR-26a-CD36 pathway mediated lipid accumulation induced by PM₂.₅ liposoluble extracts in hepatocytes. Lipid accumulation and inflammation induced by PM₂.₅ liposoluble extracts implied the potential role of PM₂.₅ in developing NAFLD.
Afficher plus [+] Moins [-]Integrative transcriptomic and protein analysis of human bronchial BEAS-2B exposed to seasonal urban particulate matter Texte intégral
2016
Longhin, Eleonora | Capasso, Laura | Battaglia, Cristina | Proverbio, Maria Carla | Cosentino, Cristina | Cifola, Ingrid | Mangano, Eleonora | Camatini, Marina | Gualtieri, M. (Maurizio)
Exposure to particulate matter (PM) is associated with various health effects. Physico-chemical properties influence the toxicological impact of PM, nonetheless the mechanisms underlying PM-induced effects are not completely understood.Human bronchial epithelial cells were used to analyse the pathways activated after exposure to summer and winter urban PM and to identify possible markers of exposure.BEAS-2B cells were exposed for 24 h to 10 μg/cm² of winter PM2.5 (wPM) and summer PM10 (sPM) sampled in Milan. A microarray technology was used to profile the cells gene expression. Genes and microRNAs were analyzed by bioinformatics technique to identify pathways involved in cellular responses. Selected genes and pathways were validated at protein level (western blot, membrane protein arrays and ELISA).The molecular networks activated by the two PM evidenced a correlation among oxidative stress, inflammation and DNA damage responses. sPM induced the release of pro-inflammatory mediators, although miR-146a and genes related to inflammation resulted up-regulated by both PM. Moreover both PM affected a set of genes, proteins and miRNAs related to antioxidant responses, cancer development, extracellular matrix remodeling and cytoskeleton organization, while miR-29c, implicated in epigenetic modification, resulted up-regulated only by wPM. sPM effects may be related to biological and inorganic components, while wPM apparently related to the high content of organic compounds.These results may be helpful for the individuation of biomarkers for PM exposure, linked to the specific PM physico-chemical properties.
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