MicroRNA-378 inhibits the development of smoking-induced COPD by targeting TNF-α

J.-L. Zhang, C.-Q. Yang, F. Deng

Department of General Medicine, Hanchuan People’s Hospital of Hubei Province, Hanchuan, China. 25884514@qq.com

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• Respiratory Medicine

OBJECTIVE: To explore the mechanism microRNA-378 in smoking-induced airway inflammation and mucus hypersecretion.
MATERIALS AND METHODS: Human bronchial epithelial (HBE) cells were treated with cigarette smoke extract (CSE) to construct the in vitro COPD model. Expression levels of microRNA-378, inflammatory factors and MUC5AC in CSE-treated HBE cells were determined by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and enzyme-linked immunosorbent assay (ELISA). The regulatory effects of microRNA-378 on expressions of inflammatory factors and mucin 5AC (MUC5AC) were observed in CSE-treated HBE cells overexpressing microRNA-378. We verified whether tumor necrosis factor-α (TNF-α) was the target gene of microRNA-378 through dual-luciferase reporter gene assay. Expression levels of TNF-α and p-p65 in CSE-treated HBE cells were examined. Finally, CSE-treated HBE cells were co-overexpressed with microRNA-378 and TNF-α to elucidate whether microRNA-378 exerted its function in regulating the development of COPD through targeting TNF-α.
RESULTS: CSE treatment downregulated microRNA-378 expression, but upregulated expressions of inflammatory factors and MUC5AC in HBE cells. MicroRNA-378 overexpression markedly inhibited the elevated levels of inflammatory factors and MUC5AC in CSE-treated HBE cells. Dual-luciferase reporter gene assay verified that TNF-α was the target gene of microRNA-378. Moreover, TNF-α expression in CSE-treated HBE cells was time-dependently elevated. TNF-α overexpression partially reversed the decreased levels of inflammatory factors and MUC5AC in HBE cells overexpressing microRNA-378.
CONCLUSIONS: MicroRNA-378 inhibits the inflammatory response by targeting TNF-α, which may be a potential therapeutic target for COPD.

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