MicroRNA-98-5p Inhibits IL-13-Induced Proliferation and Migration of Human Airway Smooth Muscle Cells by Targeting RAC1

Abstract

The dysfunction of airway smooth muscle cells (ASMCs) is one of the key factors in the pathogenesis of asthma. How miR-98-5p works in asthma has not been completely elucidated. This work focused on how miR-98-5p functions in the proliferation and migration of human ASMCs treated with interleukin-13 (IL-13). MiR-98-5p expression in plasma of asthmatic patients and IL-13-stimulated ASMCs was probed by quantitative real-time polymerase chain reaction (qRT-PCR). RAS-relevant C3 botulinum toxin substrate 1 (RAC1) protein expression in ASMCs was assessed by Western blot. The growth of ASMCs was measured by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. The migration of ASMCs was examined by Transwell assay. Besides, the apoptosis of ASMCs was analyzed by flow cytometry. The targeting relationship between miR-98-5p and RAC1 3'-UTR was verified by a dual-luciferase reporter gene assay. MiR-98-5p expression was reduced in patients' plasma and IL-13-stimulated ASMCs, and RAC1 expression was upregulated in ASMCs treated with IL-13. MiR-98-5p overexpression inhibited IL-13-induced proliferation and migration of ASMCs while promoting the apoptosis. The opposite result was observed after inhibiting miR-98-5p expression. Besides, RAC1 was identified as a direct downstream target of miR-98-5p in ASMCs. The restoration of RAC1 expression counteracted the impacts of miR-98-5p overexpression on IL-13-stimulated proliferation, migration, and apoptosis of ASMCs. MiR-98-5p inhibits IL-13-induced proliferation and migration and accelerates the apoptosis of ASMCs by downregulating RAC1 expression.

Keywords: RAC1; airway smooth muscle cells; asthma; growth; miR-98-5p; migration..