Background: Long non-coding RNA myocardial infarction associated transcript (MIAT) has exerted significant effects on atherosclerosis (AS). The biological roles of MIAT in endothelial cell dysfunction are not thoroughly elucidated.
Methods: The expression of MIAT, microRNA (miR)-206 and Ras-related protein Rab-22A (RAB22A) was detected by quantitative real-time polymerase chain reaction and western blot. The injury of human umbilical vein endothelial cells (HUVECs) was evaluated by testing cell viability, invasion, migration, apoptosis, epithelial-mesenchymal transition capacities and inflammatory response using cell counting kit-8, transwell, wound healing assays, flow cytometry, western blot and enzyme-linked immunosorbent assay, respectively. The binding interaction between miR-206 and MIAT or RAB22A was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays.
Results: The expression of MIAT was up-regulated in ox-LDL-treated HUVECs, and knockdown of MIAT in ox-LDL-treated HUVECs remarkably promoted cell viability, invasion, migration, and epithelial-mesenchymal transition (EMT), as well as suppressed cell apoptosis and the levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and endothelial nitric oxide synthase (eNOS). In a mechanical study, MIAT directly targeted miR-206, and miR-206 inhibition attenuated the protective effects of MIAT knockdown on ox-LDL-triggered HUVEC injury. Besides that, RAB22A was a target of miR-206, and RAB22A overexpression reversed the biological effects of miR-206 on ox-LDL-treated HUVECs. Additionally, we also proved MIAT could regulate RAB22A via miR-206 in HUVECs.
Conclusion: MIAT knockdown impaired ox-LDL-induced HUVEC injury via regulating miR-206/RAB22A axis, suggesting the potential impacts of MIAT on AS occurrence, which revealed a potential therapeutic strategy for future clinic intervention in AS.
Keywords: Endothelial cell; MIAT; RAB22A; miR-206; ox-LDL.
Copyright © 2021. Published by Elsevier Inc.