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

Asbestos 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-5A SETD2-KO ) were established and exposed with crocidolite, an amphibole asbestos. Cell viability of Met-5A SETD2-KO appeared to dramatically decrease with ≥ 2.5 μg/cm 2 crocidolite exposure as compared to Met-5A, although no cytotoxicity and apoptosis changes of Met-5A SETD2-KO and Met-5A was evident with 1.25 μg/cm 2 crocidolite exposure for 48 h. RNA sequencing uncovered top 50 differentially expressed genes (DEGs) between 1.25 μg/cm 2 crocidolite exposed Met-5A SETD2-KO (Cro-Met-5A SETD2-KO ) and 1.25 μg/cm 2 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-5A SETD2-KO had strong migration but mild adhesion behavior as compared to Cro-Met-5A. Additionally, crocidolite tended to increase migration of Met-5A SETD2-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 may affect adhesion-related gene expression and modify adhesion and migration behavior for SETD2-depleted Met-5A, which could provide preliminary insight regarding the potential role of SETD2 in cell behavior of asbestos-related malignant mesothelial cell.