CeRNA-based regulatory mechanisms underlying the antioxidant action of quercetin in ox-LDL-induced HUVECs damage: Roles of MALAT1 in PTEN/PI3K/AKT signaling pathway

• Published in: Food chemistry advances 2024-06, Vol.4, p.100665, Article 100665
• Main Authors: Jiang, Yang, Guan, Hui, Rong, Xue, Liu, Hui, Hao, Rili, Li, Feng, Li, Dapeng
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Endothelial cell; Non-coding rnas; Oxidative stress; Quercetin
• ISSN: 2772-753X; 2772-753X
• DOI: 10.1016/j.focha.2024.100665

•Quercetin protects HUVECs by reducing oxidative stress.•Quercetin regulated PTEN/PI3K/AKT signaling pathway.•PTEN was a target of MALAT1/miR-494–3p axis mediate the protective effect. The oxidative damage induced by oxidized low-density lipoprotein (ox-LDL) plays a pivotal role in the development of atherosclerosis. In this study, we investigated the protective effects of quercetin, a plant-derived flavonoid, against ox-LDL-induced damage in human umbilical vein endothelial cells (HUVECs) by mitigating oxidative stress. Our findings demonstrate that quercetin substantially enhances cell viability by attenuating oxidative stress induced by ox-LDL (the cell viability increased from 48 % to 89 %). Notably, this process is intricately regulated by the MALAT1/miR-494–3p/PTEN axis. In HUVECs exposed to ox-LDL, interventions such as knocking down MALAT1 or overexpressing miR-494–3p result in increased cell viability and reduced accumulation of reactive oxygen species (ROS), akin to the protective effect observed with quercetin pretreatment. Through further exploration using molecular biological technique, MALAT1 was confirmed to interact with miR-494–3p and serve as a competing endogenous RNA (ceRNA). These results, for the first time, underscore the involvement of the MALAT1/miR-494–3p/PTEN axis in quercetin's protective action against ox-LDL-induced oxidative stress. Our research provides compelling evidence supporting quercetin as a potential candidate for anti-atherosclerotic therapy. Furthermore, it offers fresh insights into the pathogenesis of atherosclerosis and potential strategies for intervention in this condition. [Display omitted]