Unveiling the molecular responses of human lung cells to retene: Transcriptomics insights and implications for toxicity

Abstract

While retene (RET) ecotoxicity has been studied, its molecular mechanisms remain unclear despite its prevalence in forest fires. This study investigated RET’s effects in BEAS-2B cells using whole transcriptome (RNA-seq) analysis, cell viability, ATP level, cell adhesion, cell migration, and cell invasiveness endpoints after 24 h and 72 h of exposure. RNA-seq revealed dynamic transcriptional changes, including dysregulated long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and pseudogenes. Pathway analysis implicated disrupted fatty acid metabolism and mitochondrial function, suggesting energy imbalance. RET induced hormesis effects, with low doses stimulating cell proliferation and increase in ATP levels. Altered cytoskeletal and extracellular matrix genes likely drove enhanced adhesion, migration, and invasiveness. Wound healing and transwell assays suggested RET may promote epithelial-mesenchymal transition-like functional phenotype (EMT). The present findings suggested metabolic adaptation and transcriptional regulation as key to RET’s effects on proliferation and invasiveness, revealing complex cellular responses to environmental stressors with implications for PAH-linked respiratory diseases and carcinogenesis.