Lnc-IL7R alleviates PM2.5-mediated cellular senescence and apoptosis through EZH2 recruitment in chronic obstructive pulmonary disease.

Background: Long-term exposure to PM_2.5 (particulate matter with an aerodynamic diameter of ≤ 2.5 μm) is associated with pulmonary injury and emphysema in patients with chronic obstructive pulmonary disease (COPD). We investigated mechanisms through which the long noncoding RNA lnc-IL7R contributes to cellular damage by inducing oxidative stress in COPD patients exposed to PM_2.5. Methods: Associations of serum lnc-IL7R levels with lung function, emphysema, and previous PM_2.5 exposure in COPD patients were analyzed. Reactive oxygen species and lnc-IL7R levels were measured in PM_2.5-treated cells. The levels of lnc-IL7R and cellular senescence–associated genes, namely p16^INK4a and p21^CIP1/WAF1, were determined through lung tissue section staining. The effects of p16^INK4a or p21^CIP1/WAF1 regulation were examined by performing lnc-IL7R overexpression and knockdown assays. The functions of lnc-IL7R-mediated cell proliferation, cell cycle, senescence, colony formation, and apoptosis were examined in cells treated with PM_2.5. Chromatin immunoprecipitation assays were conducted to investigate the epigenetic regulation of p21^CIP1/WAF1. Results: Lnc-IL7R levels decreased in COPD patients and were negatively correlated with emphysema or PM_2.5 exposure. Lnc-IL7R levels were upregulated in normal lung epithelial cells but not in COPD cells exposed to PM_2.5. Lower lnc-IL7R expression in PM_2.5-treated cells induced p16^INK4a and p21^CIP1/WAF1 expression by increasing oxidative stress. Higher lnc-IL7R expression protected against cellular senescence and apoptosis, whereas lower lnc-IL7R expression augmented injury in PM_2.5-treated cells. Lnc-IL7R and the enhancer of zeste homolog 2 (EZH2) synergistically suppressed p21^CIP1/WAF1 expression through epigenetic modulation. Conclusion: Lnc-IL7R attenuates PM_2.5-mediated p21^CIP1/WAF1 expression through EZH2 recruitment, and its dysfunction may augment cellular injury in COPD. [ABSTRACT FROM AUTHOR]