Table 1.

The role of miRNAs in the pathogenesis of asthma

MiRNA	Unusual expression	Targets	Function	References
Immune cells
Th2 cells
miR-155	Up	CTLA-4	Enhances the secretion of IL-4, -5, -13, -17a; enhances mucus secretion; stimulates T-cell activation and proliferative response	[20,27]
miR-1	Down	-	Inhibits the secretion of IL-4, -5, -8, TNF-α; regulates Th1/Th2 balance	[25]
miR-21	Up	IL-12p35 3ʹUTR	Modulates Th1/Th2 polarization	[31]
miR-3162-3p	Up	β-catenin	Enhances bronchial hyperresponsiveness and airway inflammation; regulates Th1/Th2 balance	[34]
miR-1165-3p	Up	IL-13,PPM1A	Inhibits bronchial hyperresponsiveness, airway inflammation, and differentiation of T cells toward Th2	[35]
miR-200a /200b	Down	ORMDL3	Inhibits the secretion of TNF-α, IL-4, -5, -13, and -1β	[36]
Eosinophils
miR-30a-3p	Down	CCR3	Inhibits the secretion of specific IgE, eotaxin-1, IL-5, and IL-4	[39]
miR-218-5p	Down	CTNND2	Inhibits bronchial hyperresponsiveness, eosinophilic airway inflammation, and the expression of CCL26	[41]
miR-135b	Down	CXCL12	Inhibits the immune response of Th17 cells, goblet cell proliferation, and bronchial hyperresponsiveness; reduces the number of eosinophils and lymphocytes	[42]
miR-135a	Down	The STAT family	Inhibits bronchial hyperresponsiveness and lung pathological changes; reduces the secretion of TNF-α, IL-6, IL-5, and Eotaxin	[43]
Mast cells
miR-221	Up	P27KIP1; PTEN and the p38/NF-κB pathway	Reduces the permeability of inflammatory cells, regulates the cell cycle of mast cells, and promotes their proliferation; increases the secretion of IL-4 and promotes the differentiation of Th cells into Th2 cells	[44–46]
miRNA-142-3p	Up	LPP	Enhances FceRI-mediated degranulation and rescues the reduction of degranulation	[47]
miRNA-126	Up	DNMT1	Increases the number of mast cells	[48]
Neutrophils
miR-629-3p	Up	IL-8 mRNA	Increases the levels of IL-1β and IL-8 protein, which is positively correlated with the increase of neutrophils in sputum	[49]
miR-223	Up	NLRP3	Inhibits the airway inflammation, NLRP3 level and IL-1β release	[51]
Macrophages
miR-142-5p	Up	SOCS1	Modulates the M2 polarization and profibrotic activities	[55]
miR-130a-3p	Down	Proliferator-activated receptor γ	Modulates the M2 polarization and profibrotic activities	[55]
Bronchial smooth muscle cells
miR-26a	Up	GSK-3β	Promotes ASMCs hypertrophy	[57]
miR-378	Up	The genes related to ErbB, RAS, MAPK and calcium signaling pathway	Promotes ASMCs proliferation and apoptosis resistance	[59]
miR-19a	Up	PTEN	Inhibits ASMCs proliferation and migration	[60]
miR-943-3p	Up	SFRP4	Increases the number of macrophages, eosinophils, lymphocytes, and neutrophils, increases the expression of collagen, β-catenin, and c-Myc in lung tissue, and promotes subepithelial fibrosis and ASMCs proliferation	[61]
miR-142	Down	The genes related to EGFR signaling pathway	Inhibits the proliferation of ASMCs and promotes their apoptosis	[62]
miR-204-5p	Down	SIX1	Inhibits ASMCs proliferation and extracellular matrix production	[63]
Bronchial epithelial cells
miR-744	Down	TGF-β1	Inhibits bronchial epithelial cell proliferation	[119]
miR-141	Up	CLCA1	Stimulates IL-13-induced goblet cell metaplasia, promotes airway remodeling and pathological airway mucus production	[67]
miR-146a	Up	IRAK1, TRAF6, FOXO3, PDE7A	Promotes pulmonary mucin deposition, airway remodeling, IgE synthesis, and eosinophilic inflammation	[68,69]
miR-210	Down	FOXP3	Involves in the polarization of Th2 cells	[72]
miR-34a	Down	The genes related to Wnt signaling pathway	Involves in the polarization of Th2 cells	[72]