摘要：
Human bronchial epithelial (HBE) cells and c-fos-silenced HBE cells were first exposed to fine particulate matter (PM2.5) and the resulting miRNA sequenced. Thereafter, a weighted gene co-expression network analysis was performed using Cytoscape software to visualize the interactions between identified hub miRNAs and their target genes. Nine differentially expressed miRNAs in hub miRNAs were identified in the different treatment groups, of which miR-25-3p, miR-215-5p, and miR-145-5p were selected for further study. Following qPCR validation, both miR-25-3p and miR-215-5p were found to be significantly up-regulated whilst, miR-145-5p was significantly down-regulated (p < 0.05) in the PM2.5 group. Furthermore, miR-25-3p and miR-145-5p were also significantly down-regulated in the untreated group of c-fos silenced HBE cells. However, miR-215-5p was significantly down-regulated in both the untreated and PM2.5-treated groups of c-fos silenced HBE cells. Subsequent analysis of their target genes also illustrated differential gene expression when comparing the treatment groups of the two cell types. The present data indicated that the c-fos gene has an important effect on the miRNA expression profiles and the related signaling pathways in PM2.5-treated HBE cells. Therefore, each of miR-25-3p, miR-145-5p, and miR-215-5p may potentially provide future research information for additional exploration of a PM2.5-induced carcinogenesis mechanism.
摘要：
Objective To screen the differentially expressed proteins (DEPs) in human bronchial epithelial cells (HBE) treated with atmospheric fine particulate matter (PM2.5). Methods HBE cells were treated with PM2.5 samples from Shenzhen and Taiyuan for 24 h. To detect overall protein expression, the Q Exactive mass spectrometer was used. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Perseus software were used to screen DEPs. Results Overall, 67 DEPs were screened in the Shenzhen sample-treated group, of which 46 were upregulated and 21 were downregulated. In total, 252 DEPs were screened in the Taiyuan sample-treated group, of which 134 were upregulated and 118 were downregulated. KEGG analysis demonstrated that DEPs were mainly enriched in ubiquitin-mediated proteolysis and HIF-1 signal pathways in Shenzhen PM2.5 samples-treated group. The GO analysis demonstrated that Shenzhen sample-induced DEPs were mainly involved in the biological process for absorption of various metal ions and cell components. The Taiyuan PM2.5-induced DEPs were mainly involved in biological processes of protein aggregation regulation and molecular function of oxidase activity. Additionally, three important DEPs, including ANXA2, DIABLO, and AIMP1, were screened. Conclusion Our findings provide a valuable basis for further evaluation of PM2.5-associated carcinogenesis.
通讯机构：
[Long, Ding-Xin] U;Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.
关键词：
autophagy;OPIDN;protein kinase C alpha;tri-ortho-cresyl phosphate;ubiquitin-proteasome system
摘要：
As an organophosphorus ester, tri-ortho-cresyl phosphate (TOCP) has been widely used in agriculture and industry. It is reported that TOCP can induce organophosphate-induced delayed neuropathy (OPIDN) in sensitive animal and human species. However, the exact molecular mechanisms underlying TOCP-induced neurotoxicity are still unknown. In this study, we found that TOCP could induce autophagy by activating protein kinase C alpha (PKC alpha) signaling in neuroblastoma SK-N-SH cells. PKC alpha activators could positively regulate TOCP-induced autophagy by increasing the expression levels of neighbor BRCA1 gene protein 1 (NBR1), LC3 and P62 autophagic receptor protein. Furthermore, PKC alpha activation impaired the ubiquitin-proteasome system (UPS), resulting in inhibition of proteasome activity and accumulation of ubiquitinated proteins. UPS dysfunction could stimulate autophagy to serve as a compensatory pathway, which contributed to the accumulation of the abnormally hyperphosphorylated tau proteins and degradation of impaired proteins of the MAP 2 and NF-H families in neurodegenerative disorders.
摘要：
This current study explored the effects of fine particulate matter (PM2.5) on deoxyribonucleic acid methylation in human bronchial epithelial cells. Human bronchial epithelial cells were exposed to PM2.5 for 24 h after which, deoxyribonucleic acid samples were extracted, and the differences between methylation sites were detected using methylation chips. Subsequent gene ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the differential methylation sites. Functional epigenetic modules analysis of the overall differential methylation site interactions was also conducted. A total of 127 differential methylation sites in 89 genes were screened in the PM2.5 10 mu g/ml group, of which 55 sites demonstrated increased methylation, with methylation levels decreasing in a further 72 sites. Following an exposure of 50 mu g/ml PM2.5, a total of 238 differentially methylated sites were screened in 168 genes, of which methylation levels increased in 127 sites, and decreased in 111. KEGG analysis showed that the top 10 enrichment pathways predominantly involve hepatocellular carcinoma pathways and endometrial cancer pathways, whereas functional epigenetic modules analysis screened eight genes (A2M, IL23A, TPIP6, IL27, MYD88, ILE2B, NLRC4, TNF) with the most interactions. Our results indicate that exposure to PM2.5 for 24 h in human bronchial epithelial cells induces marked changes in deoxyribonucleic acid methylation of multiple genes involved in apoptosis and carcinogenesis pathways, these findings can provide a new direction for further study of PM2.5 carcinogenic biomarkers.
