LncRNA MIR155HG contributes to smoke-related chronic obstructive pulmonary disease by targeting miR-128-5p/BRD4 axis

Area of Science:

• Pulmonary Medicine
• Molecular Biology
• Genetics

Background:

• Chronic obstructive pulmonary disease (COPD) involves exaggerated pulmonary inflammation.
• The role of long noncoding MIR155 host gene (lncRNA MIR155HG) in cigarette smoke-induced COPD is not fully understood.
• lncRNA MIR155HG is implicated in macrophage polarization in COPD.

Purpose of the Study:

• To investigate the function of lncRNA MIR155HG in cigarette smoke (CS)-mediated COPD.
• To elucidate the molecular mechanism involving MIR155HG, miR-218-5p, and BRD4 in COPD pathogenesis.
• To explore potential therapeutic strategies for COPD based on the MIR155HG/miR-218-5p/BRD4 axis.

Main Methods:

• Quantified MIR155HG and miR-218-5p expression in lung tissues and human pulmonary microvascular endothelial cells (HPMECs) exposed to cigarette smoke extract (CSE).
• Performed functional experiments including MIR155HG deletion and miR-218-5p inhibition/overexpression in HPMECs.
• Utilized dual-luciferase reporter assays and co-expression analysis to confirm molecular interactions.

Main Results:

• MIR155HG expression was upregulated, and miR-218-5p was downregulated in smokers and CSE-treated HPMECs.
• MIR155HG deletion reversed CSE-induced apoptosis and inflammation in HPMECs.
• MIR155HG targets miR-218-5p, which in turn targets BRD4, mediating CSE-induced HPMEC injury.

Conclusions:

• MIR155HG promotes apoptosis and inflammation in HPMECs in smoke-related COPD.
• The MIR155HG/miR-218-5p/BRD4 axis plays a crucial role in COPD pathogenesis.
• This pathway represents a potential therapeutic target for COPD treatment.