RNA Sequencing Analyses Reveal the Potential Mechanism of Pulmonary Injury Induced by Gallium Arsenide Particles in Human Bronchial Epithelioid Cells

Abstract

Extensive use of gallium arsenide (GaAs) has led to increased exposure to humans working in the semiconductor industry. this study employed physicochemical characterization of GaAs obtained from a workplace, cytotoxicity analysis of damage induced by GaAs in 16HBE cells, RNA-seq and related bioinformatic analysis, qRT-PCR verification and survival analysis to comprehensively understand the potential mechanism leading to lung toxicity induced by GaAs. We found that GaAs-induced abnormal gene expression was mainly related to the cellular response to chemical stimuli, the regulation of signalling, cell differentiation and the cell cycle, which are involved in transcriptional misregulation in cancer, the MAPK signalling pathway, the TGF-β signalling pathway and pulmonary disease-related pathways. Ten upregulated genes (FOS, JUN, HSP90AA1, CDKN1A, ESR1, MYC, RAC1, CTNNB1, MAPK8 and FOXO1) and 7 downregulated genes (TP53, AKT1, NFKB1, SMAD3, CDK1, E2F1 and PLK1) related to GaAs-induced pulmonary toxicity were identified. High expression of HSP90AA1, RAC1 and CDKN1A was significantly associated with a lower rate of overall survival in lung cancers. The results of this study indicate that GaAs-associated toxicities affected the misregulation of oncogenes and tumour suppressing genes, activation of the TGF-β/MAPK pathway, and regulation of cell differentiation and the cell cycle. These results help to elucidate the molecular mechanism underlying GaAs-induced pulmonary injury.

LncRNA CASC2 is involved in the development of chronic obstructive pulmonary disease via targeting miR-18a-5p/IGF1 axis

“… 1 In the present study, the human bronchial epithelial cell line 16HBE was recruited for cell experiments, which has been widely used for COPD study in previous researches. 19 , 20 It was found that low expression of CASC2 was detected in both cell and cellular medium of CSE treated 16HBE cells, which was consistent with the results shown in the clinical serum samples. It is known that miRNAs are produced by all cell types, and the same miRNA may be derived from a variety of cell sources, such as endothelial cells, monocytes and macrophages, vascular smooth cells, and platelets, and eventually are secreted in blood.…”