MiR-138 suppresses airway smooth muscle cell proliferation through the PI3K/AKT signaling pathway by targeting PDK1

ABSTRACT

Background: Airway smooth muscle cells (ASMCs) play important physiological roles in the lung, and their abnormal proliferation directly contributes to airway remodeling during development of lung diseases such as asthma. MicroRNAs are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation, but little is known about the precise role of microRNAs in the proliferation of ASMCs. Methods: In this study, human ASMCs from asthmatic and non-asthmatic donors were used. MicroRNA and mRNA expression were measured by quantitative real-time PCR. Dual-luciferase reporter assays were performed to determine whether microRNA-138 (miR-138) binds directly to 3-phosphoinositide-dependent protein kinase-1(PDK1) 3′ untranslated region (3′-UTR) to alter gene expression. Results: The results showed that overexpression of miR-138 reduced proliferation of human ASMCs, whereas inhibition of miR-138 increased proliferation of ASMCs. MiR-138 directly suppressed PDK1 expression by targeting the 3′-UTR of the gene. MiR-138 controls ASMC proliferation through directly inhibiting the phosphoinositide 3-kinase (PI3K) pathway. Conclusions: Our study indicated that miR-138 regulation of PI3K signaling in ASMCs by altering the expression of PDK1 can have a profound impact on cell proliferation.

KEYWORDS :

• airway smooth muscle cells (ASMCs)
• miR-138
• 3-phosphoinositide-dependent protein kinase-1 (PDK1)
• phosphoinositide 3–kinase/protein kinase B (PI3K/AKT) signaling pathway