TY  - EJOU
AU  - Wu, Jingjing 
AU  - Wang, Jing 
AU  - Wan, Yufeng 
AU  - Li, Yue 

TI  - Effect of LncRNA UFC1 Downregulation on Alleviating Glucocorticoid Resistance in Chronic Obstructive Pulmonary Disease via the PI3K/AKT Pathway
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - <b>Background:</b> Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease frequently complicated by glucocorticoid (GC) resistance. This study investigated whether lncRNA UFC1 regulates cigarette smoke extract (CSE)-induced inflammation, apoptosis, and GC resistance through phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling. <b>Methods:</b> To simulate cellular damage and GC insensitivity <i>in vitro</i>, U937 cells were subjected to CSE stimulation. The influence of lncRNA UFC1 silencing on cell survival, inflammatory responses, apoptosis, and GC responsiveness was evaluated through a combination of Cell Counting Kit-8 (CCK-8), reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, flow cytometry, and immunofluorescence assays. The PI3K activator 740Y-P was used for validation. <i>In vivo</i>, COPD rat models were induced by intermittent intratracheal lipopolysaccharide (LPS) instillation combined with chronic cigarette smoke exposure, and AAV-sh-UFC1 and dexamethasone (DEX) were used to evaluate lung injury, inflammation, and molecular expression. <b>Results:</b> CSE upregulated UFC1 and induced inflammation, apoptosis, and GC resistance in U937 cells. UFC1 knockdown improved cell viability (<i>p</i> &lt; 0.01); reduced IL-6, IL-1β, TNF-α, IL-8, GM-CSF, and MIP-3α levels; decreased apoptosis (<i>p</i> &lt; 0.01); and enhanced DEX sensitivity (<i>p</i> &lt; 0.01), with increased GRα and HDAC2 and decreased GRβ expression. Mechanistically, UFC1 downregulation inhibited PI3K/AKT activation (both <i>p</i> &lt; 0.001), while 740Y-P partially reversed these effects (both <i>p</i> &lt; 0.05). <i>In vivo</i> experiments confirmed that inhibiting Ufc1 attenuated lung injury and inflammation (<i>p</i> &lt; 0.01 vs. COPD + AAV-NC), improved GC resistance indicators, and inhibited PI3K/AKT activation (both <i>p</i> &lt; 0.01 vs. COPD + AAV-NC). <b>Conclusion:</b> Downregulation of lncRNA UFC1 alleviated CSE-induced inflammation, apoptosis, and GC resistance and COPD-related injury, potentially through PI3K/AKT inhibition, suggesting lncRNA UFC1 as a potential target for GC-resistant COPD.
KW  - Long non-coding RNA UFC1; pulmonary disease; chronic obstructive; glucocorticoid resistance; phosphatidylinositol 3-kinase/protein kinase b signaling pathway; inflammation; apoptosis

DO  - 10.32604/biocell.2026.086220