Abstract
BACKGROUND To study the role of the long-chain noncoding RNA (lncRNA) metastasis-related lung adenocarcinoma transcript 1 (MALAT1), microRNA-503 (miR-503), Toll-like receptor 4 (TLR4) signal axis in the pathogenesis of pulmonary arterial hypertension (PAH). MATERIAL AND METHODS Total RNA was extracted from the plasma of 45 PAH patients and 45 healthy subjects, and the expression of lncRNA MALAT1 and miR-503 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of lncRNA MALAT1 and miR-503 on Toll-like receptor 4 (TLR4) and the proliferation, migration, and apoptosis of human pulmonary artery smooth muscle cells (hPASMCs) were tested following in vitro transfection of hPASMCs. RESULTS lncRNA MALAT1 was highly expressed in the plasma of PAH patients and in hypoxia-induced hPASMCs. Silencing lncRNA MALAT1 inhibited the proliferation and migration of hPASMC cells while promoting their apoptosis. MiR-503 is underexpressed in plasma and hPASMCs of patients with PAH. TLR4 was a target gene of miR-503 and was highly expressed in peripheral blood mononuclear cells (PBMCs) of PAH patients. lncRNA MALAT1 was a "molecular sponge" of miR-503, regulating the expression of TLR4 and the proliferation, migration, and apoptosis of hPASMCs through miR-503. CONCLUSIONS lncRNA MALAT1 promotes the proliferation and migration of hPASMCs and inhibits their apoptosis by inhibiting the miR-503/TLR4 signal axis.