MiR-21 modulates human airway smooth muscle cell proliferation and migration in asthma through regulation of PTEN expression

Abstract

<div><p>ABSTRACT</p><p><i>Background:</i> Asthma is characterized by airway remodeling arising from an increase in airway smooth muscle (ASM) mass. This increase is regulated in part by ASM cell proliferation and migration. MicroRNA (miR)-21 also plays a role in asthma, but the molecular mechanisms underlying its effects are not completely understood. This study investigated the effects and mechanism of miR-21 on the human ASM (HASM) cell proliferation and migration. <i>Materials and Methods:</i> HASM cells were transduced with a miR-21 vector, and the expression of miR-21 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of the miR-21 on HASM cell proliferation and migration was analyzed by CCK8 and transwell assay. The expression level of <i>PTEN</i> (phosphatase and tensin homolog deleted on chromosome 10) in HASM cells was assessed by qRT-PCR and Western blot analysis. Meanwhile, the activity of PTEN was measured by PTEN malachite green assay kit. <i>Results:</i> Lentivirus-mediated miR-21 overexpression markedly enhanced the proliferation and migration of HASM cells (<i>P</i> < .05), and ablation of miR-21 by anti-miR-21 inhibitor markedly reduced cell proliferation and migration. We demonstrated that miR-21 overexpression significantly reduced the expression of PTEN (<i>P</i> < .05), while PTEN knock-down markedly increased HASM cell proliferation and migration. Furthermore, we found that overexpression of PTEN led to a decrease of HASM cell proliferation and migration. MiR-21 mediated HASM cell proliferation and migration through activation of the phosphoinositide 3-kinase pathway. <i>Conclusions:</i> This study provides the first <i>in vitro</i> evidence that overexpression of miR-21 in HASM cells can trigger cell proliferation and migration, and the effects of miR-21 depend on the level of PTEN.</p></div