Disease relevant modifications of the methylome and transcriptome by particulate matter (PM_2.5) from biomass combustion

Abstract

Exposure to particulate matter (PM) is recognized as a major health hazard, but molecular responses are still insufficiently described. We analyzed the epigenetic impact of ambient PM2.5 from biomass combustion on the methylome of primary human bronchial epithelial BEAS-2B cells using the Illumina HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix HG-U133 Plus 2.0 Array. PM2.5 induced genome wide alterations of the DNA methylation pattern, including differentially methylated CpGs in the promoter region associated with CpG islands. Gene ontology analysis revealed that differentially methylated genes were significantly clustered in pathways associated with the extracellular matrix, cellular adhesion, function of GTPases, and responses to extracellular stimuli, or were involved in ion binding and shuttling. Differential methylations also affected tandem repeats. Additionally, 45 different miRNA CpG loci showed differential DNA methylation, most of them proximal to their promoter. These miRNAs are functionally relevant for lung cancer, inflammation, asthma, and other PM-associated diseases. Correlation of the methylome and transcriptome demonstrated a clear bias toward transcriptional activation by hypomethylation. Genes that exhibited both differential methylation and expression were functionally linked to cytokine and immune responses, cellular motility, angiogenesis, inflammation, wound healing, cell growth, differentiation and development, or responses to exogenous matter. Disease ontology of differentially methylated and expressed genes indicated their prominent role in lung cancer and their participation in dominant cancer related signaling pathways. Thus, in lung epithelial cells, PM2.5 alters the methylome of genes and noncoding transcripts or elements that might be relevant for PM- and lung-associated diseases.

MicroRNA‐570 is a novel regulator of cellular senescence and inflammaging

“…Previous studies have linked miR-570 expression and exposure of BEAS-2B cells to particulate matter with an aerodynamic diameter <2.5 μm. In these experiments, particulate matter with an aerodynamic diameter <2.5 μm led to hypomethylation of the transcription start site of miR-570, leading to increased expression of this miRNA species (57). These data suggest that elevated oxidative stress through cigarette smoke exposure and/or air pollution may also induce miR-570-3p in airway epithelial cells, inducing cellular senescence.…”

Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks

“…Measurement of angiogenesis from blood serum using an angiogenesis antibody array revealed increased levels of 12 angiogenesis factors in mice after PM 2.5 treatment [44]. Exposure to PM 2.5 has an impact on the methylome of primary human bronchial epithelial BEAS-2B, which impacts the expression of genes functionally linked to angiogenesis, indicating a prominent role in lung cancer signaling pathways [45].…”

“…Transition metals contained in PM 10 and PM 2.5 are partially responsible for TNF-α and IL6 release in macrophages [65]. However, other components of PM are responsible for inflammatory responses, including PAHs [26], activation of AHR [46], upregulation of CYP1A1 and CYP1B1 genes [66], hypomethylation in genes linked to cytokine and immune responses [45], upregulation of miR-146a [67], and suppression of a long non-coding RNA (lnc-PCK1-2:1) [68]. The inflammatory response induced by PM or by some PM components has been well demonstrated in several cell linages including blood mononuclear cells [69], natural killer cells [70], T cells [71], human pulmonary fibroblasts [72], but also in lung tissue of rats exposed to PM 10 [73] and circulating monocytes and T lymphocytes from humans environmentally exposed [74], as well as in BALB/c mice [75].…”

Function of PM2.5 in the pathogenesis of lung cancer and chronic airway inflammatory diseases (Review)

“…To the best of our knowledge, inactivation of other PM2.5-induced tumor suppressor genes via DNA methylation has not been demonstrated. However, a recent analysis of the methylome and transcriptome of PM2.5-induced (100 µg/ml) BEAS-2B cells identified 66 differentially expressed genes, which were either hyper-or hypo-methylated, involved in lung diseases, particularly lung cancer (47). A number of the genes were identified to be involved in tumor suppression, including deleted in malignant brain tumors 1, ERBB receptor feedback inhibitor 1 and gap junction protein β2.…”