Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disorder. N5-methylcytosine (m5C) RNA modification, catalyzed by methyltransferases such as NOP2, plays a crucial role in regulating RNA stability and gene expression. This study aims to investigate the role of NOP2 in COPD and elucidate the underlying mechanism by which NOP2 modulates COPD progression through m5C modification. Sprague-Dawley (SD) rats subjected to cigarette smoke exposure and human bronchial epithelial (HBE) cells treated with lipopolysaccharide (LPS)+cigarette smoke extract were used as in vivo and in vitro COPD models. Differentially expressed m5C regulators between COPD patients and healthy controls and targets of NOP2 were screened from GSE106986 dataset. The role of NOP2 in inflammation and apoptosis was evaluated by flow cytometry, measuring IL-6, IL-1β and TNF-α in vivo and in vitro, hematoxylin-eosin and TUNEL staining. NOP2 expression was increased in LPS-induced HBE cells and COPD rat model. NOP2 knockdown inhibited inflammation and apoptosis in LPS-induced HBE cells, reduced IL-6, IL-1β and TNF-α contents in bronchoalveolar lavage fluid and serums, and inhibited inflammatory infiltration and apoptosis in lung tissues of COPD rats. NFKB1 was positive correlated with NOP2 expression. NFKB1 overexpression restored inflammation and apoptosis inhibited by NOP2 knockdown in LPS-induced HBE cells. Mechanistically, NOP2 knockdown inhibited NFKB1 transcription by decreasing m5C modification on NFKB1. NOP2 stabilized NFKB1 expression through m5C modification, thereby participating in inflammation and apoptosis in COPD. These findings revealed a new regulatory mechanism in COPD and highlight NOP2 as a potential therapeutic target.