MiR-21 modulates proliferation and apoptosis of human airway smooth muscle cells by regulating autophagy via PARP-1/AMPK/mTOR signalling pathway

Abstract

Superfluous human airway smooth muscle (HASM) cell proliferation is an important pathological feature of airway remodelling in asthma. This study aimed to determine whether miR-21 is involved in the regulation of HASM cell survival. Overexpressed miR-21 inhibited HASM cell apoptosis and autophagy and promoted proliferation, whereas a miR-21 inhibitor exerted the opposite effects (P < 0.05). Overexpressed poly (ADP-ribose) polymerase-1 (PARP-1) promoted apoptosis and inhibited proliferation of HASM cells (P < 0.05). Dual-luciferase assays confirmed that miR-21 directly targeted poly (ADP-ribose) polymerase-1 (PARP-1) mRNA (P < 0.05). Silencing PARP-1 based on miR-21 downregulation mimicked the role of 3-methyladenine (3-MA), an autophagy inhibitor (P < 0.05). Overexpressed PARP-1 reversed the effects of miR-21 on HASM cells, somewhat dependently on PARP-1-induced enhanced autophagy, which we elucidated by 3-MA block (P < 0.05). MicroRNA-21 mimics reduced AMPK and increased mTOR signalling by downregulating PARP-1, and a miR-21 inhibitor exerted the opposite effects (P < 0.05). Collectively, miR-21 inhibitor could upregulate PARP-1 in HASM cells to promote autophagy and thus inhibit proliferation and promote apoptosis that might be mediated by the AMPK/mTOR signalling pathway.