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

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.