Background
Mounting evidence suggests that alternative splicing is one of the ways for cells to adapt to environmental stress insults. The
Conclusions
Significant changes in alternative splicing of silicosis-associated genes occur in patients with silicosis in silica conditions. Our study provides basic founding for further investigation into the detail molecular mechanisms underlying silica-induced silicosis.
Methods
Microarray analysis was used to construct the alternative splicing profile. Functional experiments were conducted using Cell Counting Kit-8, cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT) analyses. Alternative splicing variants were verified by quantitative real-time polymerase chain reaction (qRT-PCR) polymerase chain reaction method.
Results
A total of 1850 genes that have alternative splices in response to silica insult were identified. PCDHB11, MALAT1, MT2A, RP11-126D17.1, and RP11-415I12.2 are the top 5 upregulated genes with occurrence of alternative splice, whereas NDE1, RNPEPL1, TREML2, CSF2RB, and PRKCSH are the top 5 downregulated genes with occurrence of alternative splice. Bioinformatic analysis showed these genes with the occurrence of alternative splice mainly are associated with EMT pathway, N-Glycan biosynthesis, and leukocyte transendothelial migration. Further study indicated that PRKCSH-2 knockdown promotes A549 cell proliferation potential by partially promoting EMT signals. Conclusions: Significant changes in alternative splicing of silicosis-associated genes occur in patients with silicosis in silica conditions. Our study provides basic founding for further investigation into the detail molecular mechanisms underlying silica-induced silicosis.