LncRNA MEG3 aggravates acute pulmonary embolism-induced pulmonary arterial hypertension by regulating miR-34a-3p/DUSP1 axis

Acute pulmonary embolism (APE)-induced pulmonary artery hypertension (PAH) is a fatal disease. The miR-343p/DUSP1 has inhibitory effects on the thickening of the pulmonary arterial walls in APE rats and the proliferation of platelet-derived growth factor-BB (PDGF-BB)-induced human pulmonary arterial smooth muscle cells (hPASMCs). Herein, the lncRNAs regulating the miR-34a-3p/DUSP1 axis in APE and PAH are further explored in vitro and in vivo. MEG3 targeted miR-34a-3p. MEG3 overexpression potentiated the effects of PDGF-BB treatment on promoting the viability and proliferation of hPASMCs, as well as the mPAP level in APE rats. Also, overexpressed MEG3 strengthened PDGF-BB-induced upregulation of MEG3, NOR-1, PCNA and DUSP1, as well as downregulation of miR-34a-3p in hPASMCs and APE rats. However, shMEG3 generated opposite effects. MiR34a-3p mimic reversed the effect of MEG3 overexpression, and DUSP1 overexpression neutralized the effect of MEG3 downregulation on PDGF-BB-induced hPASMCs and APE rats.MEG3 aggravates APE-induced PAH by regulating miR-34a-3p/DUSP1 axis, holding a great promise as a novel biomarker for PAH treatment.