Inhibition of ox‐LDL‐induced endothelial cell injury by LINC02381 knockdown through the microRNA‐491‐5p/transcription factor 7 axis

Abstract

Atherosclerosis (AS) is a complex multifactorial and chronic inflammatory vascular disease that contributes to the development of cardiovascular diseases. Abnormal cellular proliferation in human umbilical vein endothelial cells (HUVECs) is a crucial element in AS development. In this study, we investigated the potential role of the long noncoding RNA LINC02381/ microRNA (miR)-491-5p/transcription factor 7 (TCF7) axis in regulating HUVEC injury in 30 participants suffering from AS and 30 healthy control participants. We established an in vitro model of AS in HUVECs using oxidized low-density lipoprotein (ox-LDL), and measured cellular mRNA and protein levels of LINC02381, miR-491-5p, and TCF7 in serum samples using reverse transcription-quantitative polymerase chain reaction and Western blotting assays. We evaluated cell viability, apoptosis, and inflammation using Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays, respectively. Moreover, we analyzed apoptosis-related protein expression using western blotting analysis and determined the association between miR-491-5p and LINC02381 or TCF7 using dual-luciferase reporter assay, RNA pull-down, and rescue experiments. We observed that LINC02381 was elevated, while miR-491-5p was downregulated in serum samples from participants with AS and in ox-LDL-treated HUVECs. LINC02381 knockdown was protective against HUVEC injury via miR-491-5p inhibition, which is its downstream target. Rescue experiments further demonstrated that miR-491-5p alleviated HUVEC injury by modulating TCF7. Thus, LINC02381 knockdown ameliorated HUVEC injury by regulating the miR-491-5p/TCF7 axis, which provides new insights into AS treatment strategies.

LncRNA FRMD6‐AS1/miR‐491‐5p/USP13 pathway attenuated ferroptosis and contributed to liver fibrosis

“…In this study, lncRNA FRMD6-AS1 expression was elevated in activated HSC-T6 cells, and knockdown of FRMD6-AS1 increased iron miR-491-5p can be declined by lncRNAs in cancers, brain oxidative stress after brain injury, and atherosclerosis. 41,42 By competitively binding with miR-491-5p, lncRNAs, such as lncRNA AK046375, LINC02381 and lncRNA LBX2-AS1, can modulate the progression cancers and oxidative stress. 41,42 In addition, miR-491-5p exerts Several target genes of miR-491-5p, including emilin 1, TP53 and metallothionein-2, could be dramatically repressed by miR-491-5p via binding to 3' UTRs.…”

“…41,42 By competitively binding with miR-491-5p, lncRNAs, such as lncRNA AK046375, LINC02381 and lncRNA LBX2-AS1, can modulate the progression cancers and oxidative stress. 41,42 In addition, miR-491-5p exerts Several target genes of miR-491-5p, including emilin 1, TP53 and metallothionein-2, could be dramatically repressed by miR-491-5p via binding to 3' UTRs. 24,27,41 USP13 is a deubiquitinase that modulates cancer progression, immune inflammatory response, metabolism disorder.…”