Panya Aussara, Thongyim Saruda, Sattayawat Pachara, Inwongwan Sahutchai
Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand.
Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand.
Toxics. 2025 Jun 8;13(6):484. doi: 10.3390/toxics13060484.
Acute PM2.5 exposure has been implicated in lung cancer progression, yet its impact on genetically distinct NSCLC cells remains underexplored. This study investigates how mutation-specific transcriptional responses influence susceptibility to PM2.5-induced oncogenic alterations, focusing on A549 and NCI-H1975 cells. This provides preliminary insight into the transcriptomic effects of acute PM2.5 exposure in NSCLC cells with distinct oncogenic mutations (A549 and NCI-H1975), serving as a guide for understanding mutation-specific responses to environmental stress. Cells were exposed to PM2.5 (200 µg/mL, 24 h), followed by RNA sequencing and analysis. Gene ontology and pathway enrichment analyses were conducted to identify key molecular alterations associated with tumour progression. NCI-H1975 cells exhibited a stronger transcriptional response, with a higher fold change in differentially expressed genes (DEGs), indicating greater PM2.5 susceptibility. Upregulated genes were linked to oxidative stress, carcinogen activation, metabolic reprogramming, and therapy resistance, reinforcing tumour survival under PM2.5 stress. Conversely, the downregulation of tumour suppressor genes suggests immune suppression and potential immunotherapy resistance. This study reveals that acute PM2.5 exposure induces mutation-specific transcriptomic alterations in NSCLC, with EGFR-mutant cells exhibiting heightened oxidative stress, metabolic shifts, and immune evasion. The upregulation of key genes highlights the profound molecular impact of short-term exposure, paving the way for future studies on pollution-driven oncogenic mechanisms and resistance pathways.
急性暴露于细颗粒物（PM2.5）已被认为与肺癌进展有关，但其对基因不同的非小细胞肺癌（NSCLC）细胞的影响仍未得到充分研究。本研究调查了突变特异性转录反应如何影响对PM2.5诱导的致癌改变的易感性，重点关注A549和NCI-H1975细胞。这为深入了解急性暴露于PM2.5对具有不同致癌突变（A549和NCI-H1975）的NSCLC细胞的转录组学影响提供了初步见解，为理解对环境应激的突变特异性反应提供了指导。将细胞暴露于PM2.5（200 µg/mL，24小时），随后进行RNA测序和分析。进行基因本体论和通路富集分析以确定与肿瘤进展相关的关键分子改变。NCI-Hl975细胞表现出更强的转录反应，差异表达基因（DEG）的倍数变化更高，表明对PM2.5的易感性更强。上调的基因与氧化应激、致癌物激活、代谢重编程和治疗抗性相关，增强了PM2.5应激下的肿瘤存活。相反，肿瘤抑制基因的下调表明免疫抑制和潜在的免疫治疗抗性。本研究表明，急性暴露于PM2.5会在NSCLC中诱导突变特异性转录组改变，表皮生长因子受体（EGFR）突变细胞表现出更高水平的氧化应激、代谢变化和免疫逃逸。关键基因的上调突出了短期暴露的深远分子影响，为未来关于污染驱动的致癌机制和抗性途径的研究铺平了道路。
