Characteristics of transcription profile, adhesion and migration of SETD2 ‐loss Met‐5A mesothelial cells exposed with crocidolite

AbstractAsbestos is fibrous silicate mineral exhibiting biopersistence and carcinogen property and contribute to mesothelioma. Despite the concept of gene-environmental interaction in pathogenesis of mesothelioma, the possible pathophysiological changes of mesothelial cells simultaneously with SETD2 loss and asbestos exposure remains obscure. Herein, CRISPR/Cas9-mediated SETD2 knockout Met-5A mesothelial cells (Met-5ASETD2-KO) were established and exposed with crocidolite, an amphibole asbestos. Cell viability of Met-5ASETD2-KO appeared to dramatically decrease with ≥ 2.5 μg/cm2 crocidolite exposure as compared to Met-5A, although no cytotoxicity and apoptosis changes of Met-5ASETD2-KO and Met-5A was evident with 1.25 μg/cm2 crocidolite exposure for 48 h. RNA sequencing uncovered top 50 differentially expressed genes (DEGs) between 1.25 μg/cm2 crocidolite exposed Met-5ASETD2-KO (Cro-Met-5ASETD2-KO) and 1.25 μg/cm2 crocidolite exposed Met-5A (Cro-Met-5A), and ITGA4, THBS2, MYL7, RAC2, CADM1, and CLDN11 appeared to be the primary DEGs involved with adhesion in GO and KEGG analysis. Cro-Met-5ASETD2-KO had strong migration but mild adhesion behavior as compared to Cro-Met-5A. Additionally, crocidolite tended to increase migration of Met-5ASETD2-KO but inhibited migration of Met-5A when compared to their corresponding cells without crocidolite exposure, although no further adhesion property changes was evident for both cells in response to crocidolite. Therefore, crocidolite...
Source: Journal of Applied Toxicology - Category: Toxicology Authors: Tags: RESEARCH ARTICLE Source Type: research