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.

Docosahexaenoic acid (DHA) is reported to have the potential to ameliorate pulmonary arterial hypertension (PAH), while the specific mechanism is still obscure. This study aims to investigate the function of DHA in pulmonary artery smooth muscle cells (PASMCs) and explore the underlying mechanism. In our study, DHA was used to incubate PASMCs. Cytosolic‐free Ca2+ concentration ([Ca2+]cyt) was measured using Fluo‐3 AM method. Real‐time polymerase chain reaction was used to detect microRNA‐16 (miR‐16) and calcium‐sensing receptor (CaSR) messenger RNA expression levels. CCK‐8 assay, BrdU assay, and Transwell assay were employed to detect the effects of DHA on proliferation and migration of PASMCs. CaSR was confirmed as a direct target of miR‐16 using dual‐luciferase assay, polymerase chain reaction, and Western blot analysis. It was found that DHA significantly inhibited PASMC proliferation and migration and decreased [Ca2+]cyt. After transfection of miR‐16 mimics, proliferation and migration ability of PASMCs were significantly inhibited, whereas opposite effects were observed after miR‐16 inhibition. [Ca2+]cyt was also inhibited by miR‐16 transfection. DHA then promoted the expression of miR‐16, and the effects of DHA on PASMCs were annulled when miR‐16 was inhibited. CaSR was identified as a direct target of miR‐16. CaSR was inhibited directly by miR‐16 and indirectly by DHA. In conclusion, DHA inhibits the proliferation and migration of PASMCs, and probably ameliorates PAH via regulating miR‐16/CaSR axis.