NEAT1 silencing alleviates pulmonary arterial smooth muscle cell migration and proliferation under hypoxia through regulation of miR-34a-5p/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 RT-qPCR, the expression levels of NEAT1, microRNA (miR)-34a-5p, and Kruppel-like factor 4 (KLF4) were detected in both hypoxia-treated pulmonary arterial smooth muscle cells (PASMCs) and serum from PAH patients. Then, the interactions among miR-34a-5p, NEAT1, and KLF4 were evaluated by dual-luciferase reporter assay. The detailed role of the NEAT1/miR-34a-5p/KLF4 axis in PAH pathogenesis was further explored using MTT, Transwell, and western blot assays. The results revealed that NEAT1 targeted miR-34a-5p and miR-34a-5p targeted KLF4. In hypoxia-treated PASMCs and serum from PAH patients, high NEAT1 and KLF4 expression levels and low miR-34a-5p expression were observed. The proliferation and migration of hypoxia-treated PASMCs were reduced by transfection with sh-NEAT1 or miR-34a-5p mimics. The suppressive effects of NEAT1 knockdown on the proliferation and migration of hypoxia-treated PASMCs were reversed by knock down of miR-34a-5p 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 miR-34a-5p/KLF4 in vitro. The present study highlighted a potential new therapeutic target and diagnostic biomarker for PAH.

Automated summary

NEAT1 regulates cell proliferation and migration in the pathogenesis of PAH by targeting miR-34a-5p that affects KLF4 expression levels. High levels of NEAT1 and KLF4 expression and low miR-34a-5p expression were observed in hypoxia-treated PASMCs and serum from PAH patients, indicating a potential therapeutic target and diagnostic biomarker for PAH.