Long non‑coding RNA PEG13 regulates endothelial cell senescence through the microRNA‑195/IRS1 axis

Abstract

Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction and plaque formation. The present study aimed to elucidate the pathological role of the long non‑coding RNA (lncRNA) paternally expressed 13 (PEG13) in the onset and progression of atherosclerosis. Specifically, its effects on human umbilical vein endothelial cell (HUVEC) proliferation, angiogenesis, senescence and senescence‑associated secretory phenotype (SASP)‑related factors were investigated using cell proliferation, cellular angiogenesis, β‑galactosidase staining, reverse transcription‑quantitative PCR and enzyme‑linked immunosorbent assays. The results showed that oxidized low‑density lipoprotein (ox‑LDL) inhibited lncRNA PEG13 expression and HUVEC viability in a dose‑dependent manner and PEG13 overexpression partially reversed these effects. Additionally, PEG13 overexpression ameliorated the ox‑LDL‑induced impairment of angiogenesis, cellular senescence and SASP. Furthermore, lncRNA PEG13 directly targeted microRNA (miR/miRNA)‑195‑5p, suppressing the ox‑LDL‑induced upregulation of the miRNA. The gene coding for insulin receptor substrate 1 (IRS1), an activator of the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway, was confirmed as a direct target of miR‑195. PEG13 overexpression attenuated the ox‑LDL‑induced inhibition of IRS1 expression and PI3K/AKT signaling and its protective effects on HUVEC viability, angiogenesis and senescence were partially reversed by small interfering RNAs targeting IRS1. The present study demonstrated that lncRNA PEG13 attenuates ox‑LDL‑induced senescence in HUVECs by modulating the miR‑195/IRS1/PI3K/AKT signaling pathway, suggesting a potential therapeutic target for the treatment of atherosclerosis.