Exploring the regulatory role of mtTFA on inflammation, oxidative stress, and epigenetic alterations in COPD progressed NSCLC patients with smoking history.

Oxidative stress and inflammation are pivotal in linking COPD to NSCLC progression, with dysregulated cytokine levels in inflamed COPD airways correlating with disease severity and lung cancer advancement. CD4 T helper cells, pivotal in the inflammatory response, exhibit altered gene expression patterns in COPD and NSCLC, emphasizing their role in disease pathogenesis. Mitochondrial transcription factor A (mtTFA) dysregulation is implicated in inflammation and oxidative stress, affecting COPD and NSCLC progression. CRISPR/Cas9-mediated mtTFA depletion heightens inflammatory transcription factor expression, whileitsoverexpression reduces inflammation and oxidative stress markers. Histone deacetylases (HDACs) exhibit elevated expression in COPD and NSCLC CD4 T cells, with inhibition via TSA treatment showing decreased inflammation and oxidative stress. Patients progressing from COPD to NSCLC demonstrate distinct epigeneticsignatures,with altered acetylation and methylation markers. TSA treatment enhances methylation and acetylation at the VEGFA gene locus, mitigating disease progression effects. Overexpression of mtTFA downregulates HDACs, while knockout upregulates them, influencing oxidative stress levels. These findings underscore the interplay between transcription factors, cytokines, and epigenetic regulation in CD4 T cells, providing insights into disease mechanisms and potential therapeutic avenues. Understanding these pathways and targets may lead to innovative epigenetic therapies for COPD and NSCLC, potentially preventing COPD progression to NSCLC.