MicroRNA-138 promotes proliferation and suppresses mitochondrial depolarization in human pulmonary artery smooth muscle cells through targeting TASK-1

Abstract

MicroRNA (miR)-138 serves an important role in the proliferation, differentiation and apoptosis of human pulmonary artery smooth muscle cells (HPASMCs), indicating the involvement of miR-138 in the development and progression of pulmonary artery hypertension (PAH). Potassium channel subfamily K member 3 (TASK-1), a two-pore domain K+ channel, is expressed in HPASMCs and is associated with hypoxic PAH. However, whether miR-138 mediates PAH through targeting TASK-1 is not known. In the present study, HPASMCs were transfected with miR-138 mimic to establish a PAH model in vitro, and the effects of a miR-138 inhibitor and a TASK-1 inhibitor (A293) were examined. Cell proliferation and mitochondrial membrane potential (MMP) were measured by CCK-8 assay and flow cytometry, respectively. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to examine the expression of miR-138, TASK-1, Bcl-2, caspase-3 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2). A dual-luciferase reporter assay was also used to analyse the expression level of TASK-1 in HPASMCs. The results of the present study demonstrated that the miR-138 mimic promoted proliferation and MMP level, which was similar to the effect of A293 treatment on HPASMCs. However, the miR-138 inhibitor inhibited the effects induced by miR-138 mimic or A293 treatment, as demonstrated by a decrease in proliferation and MMP level in HPASMCs, accompanied by a decrease of Bcl-2 and an increase of caspase-3 expression levels, as well as ERK1/2 activation. The dual-luciferase reporter assay indicated that TASK-1 expression was negatively regulated by miR-138. The results of the present study suggested that miR-138 promoted proliferation and suppressed mitochondrial depolarization of HPASMCs by targeting TASK-1.