NEAT1 silencing alleviates pulmonary arterial smooth muscle cell migration and proliferation under hypoxia through regulation of miR­34a­5p/KLF4 in vitro.

Pulmonary arterial hypertension (PAH) is a severe vascular disease that adversely affects patient health and can be life threatening. The present study aimed to investigate the detailed role of nuclear paraspeckle assembly transcript 1 (NEAT1) in PAH. Using RT­qPCR, the expression levels of NEAT1, microRNA (miR)­34a­5p, and Krüppel­like factor 4 (KLF4) were detected in both hypoxia­treated pulmonary arterial smooth muscle cells (PASMCs) and serum from PAH patients. Then, the interactions among miR­34a­5p, NEAT1, and KLF4 were evaluated by dual­luciferase reporter assay. The detailed role of the NEAT1/miR­34a­5p/KLF4 axis in PAH pathogenesis was further explored using MTT, Transwell, and western blot assays. The results revealed that NEAT1 targeted miR­34a­5p and miR­34a­5p targeted KLF4. In hypoxia­treated PASMCs and serum from PAH patients, high NEAT1 and KLF4 expression levels and low miR­34a­5p expression were observed. The proliferation and migration of hypoxia­treated PASMCs were reduced by transfection with sh­NEAT1 or miR­34a­5p mimics. The suppressive effects of NEAT1 knockdown on the proliferation and migration of hypoxia­treated PASMCs were reversed by knock down of miR­34a­5p expression and increased KLF4 expression. NEAT1 was not only highly expressed in the serum of PAH patients but its silencing also alleviated PAH by regulating miR­34a­5p/KLF4 in vitro. The present study highlighted a potential new therapeutic target and diagnostic biomarker for PAH.