ABSTRACT: This study investigated the toxicological effects of two short-chain per- and polyfluoroalkyl substances (PFAS), including perfluorobutanoic acid (PFBA) and perfluorohexanoic acid (PFHxA), on the transcriptome of human nasal RPMI2650 cells. Gene annotation enrichment analysis highlighted neurofactor, synaptic, solute carrier, and ribosome signaling pathways in common pathways of widespread transcriptional changes in RPMI2650 cells. Systematic analysis of RNA-seq data revealed that PFAS-treated RPMI2650 cells are encoded to participate in cell proliferation (H3C14), nerve regeneration (L1CAM, P2RY1), and solute transport (SLC17A7, LRRK2). TOP 10 GO analysis showed that DEGs was mainly concentrated in synaptic regulation, cell division correlation and solute carrier transport. For example, in the PFBA treatment group, typical terms include synaptic vesicular membrane (GO:0030672), synaptic transmission, glutaminergic energy (GO:0035249), and interneuronal synaptic transmission (GO:0007270), while in the PFHxA treatment group, DEGs is mainly enriched in nucleosomes (GO:0000786). Microtubule binding (GO:0008017) and neuronal differentiation in the central nervous system (GO:0021953). In KEGG enrichment pathway, PFBA-treated differential genes were mainly concentrated in synaptic related pathways, such as serotonergic synapses (hsa04726), glycerophospholipid metabolism (hsa00564), and GABAergic synapses (hsa04727). In addition to neuron-related pathways, PFHxA processing enrichedneurotransmitter related pathways such as sphingolipid biosynthesis-Globo and isoglobo series (hsa00603), GABaergic synapses (hsa04727), and neuroactive ligand-receptor interactions (hsa04080).
