Inhibitory Effect Of MicroRNA-638 On Proliferation And Migration Of Human Airway Smooth Muscle Cells

Background: Bronchial asthma is a type of chronic inflammatory airway responsive disease.Airway remodeling is an important pathological feature.Airway smooth muscle cell(ASMC)plays an important role in the lungs,and excessive proliferation and migration of ASMC directly leads to airway remodeling.Micro RNA(mi R)-638 is a primate-specific mi RNA that plays important roles in development,DNA damage repair,hematopoiesis,and tumorigenesis.Although it is highly expressed in ASMCs,its function in ASM remodeling remains unknown.Methods and Results: In the present study,we found that in response to various mitogenic stimuli,including PDGF-BB,TGF-?,and FBS,the expression of mi R-638,as determined by quantitative real-time polymerase chain reaction(q RT-PCR),was significantly downregulated in the proliferative human ASMCs.Both gain-and loss-of-function studies were then performed to study the role of mi R-638 in ASMC proliferation and migration.We found that adenovirus-mediated mi R-638 overexpression markedly inhibits the proliferation and migration of ASMCs,while ablation of mi R-638 by anti-mi R-638 markedly increases cell proliferation and migration,as determined by WST-8 proliferation and scratch wound assays.Dual-luciferase reporter assay,q RT-PCR,and western blot analysis were used to investigate the effects of mi R-638 on the expression of the downstream target genes in ASMCs.Furthermore,our results demonstrated that cyclin D1 and NOR1 are downstream target genes directly regulated by mi R-638,and high expression of mi R-638 significantly down-regulates the expression of cyclin D1 and NOR1,both of which have been shown to be essential for cell proliferation and migration.Conclusion: In this regard,our study provides the first in vitro evidence highlighting the anti-proliferative and anti-migratory roles of mi R-638 in human ASMC remodeling and suggests that targeted overexpression of mi R-638 in ASMCs may provide a novel therapeutic strategy for preventing ASM hyperplasia associated with asthma.