LncRNA GAS5 promotes spermidine‑induced autophagy through the miRNA‑31‑5p/NAT8L axis in pulmonary artery endothelial cells of patients with CTEPH

Chronic thromboembolic pulmonary hypertension (CTEPH) is a leading cause of pulmonary hypertension. The present study investigated the mechanisms of long non‑coding RNA growth arrest‑specific transcript 5 (GAS5) on spermidine (SP)‑induced autophagy(definition). Pulmonary artery endothelial cells (PAECs) were collected from patients with CTEPH and the rat model. Immunofluorescence, Western blots, reverse transcription‑quantitative polymerase chain reaction, bioinformatics, rapid amplification of cDNA ends assays, luciferase reporter assays, RNA‑binding protein immunoprecipitation assays, GFP‑LC3 adenoviruses, tfLC3 assays and transmission electron microscopy were performed. The results revealed that SP‑induced autophagy increased GAS5 in PAECs. The upregulation of GAS5 enhanced and the downregulation of GAS5 reversed the roles of SP in PAECs. Furthermore, GAS5 promoted SP‑induced autophagy in PAECs by targeting miRNA‑31‑5p. The miRNA‑31‑5p mimic suppressed and the inhibitor promoted SP‑induced autophagy. Furthermore, N‑Acetyltransferase 8 Like (NAT8L) was a target gene of miRNA‑31‑5p and knockdown of NAT8L inhibited the autophagic levels of PAECs. <em>In vivo</em>, SP treatment decreased miRNA‑31‑5p and increased NAT8L levels, which was reversed by the knockdown of GAS5. The downregulation of GAS5 abolished the stimulatory role of SP in PAECs of CTEPH rats. In conclusion, GAS5 promoted SP‑induced autophagy through miRNA‑31‑5p/NAT8L signaling pathways in vitro and in vivo and GAS5 may be a promising molecular marker for therapies of CTEPH.1