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LncRNA MIAT Mediates ox-LDL-Induced Endothelial Cell Injury Via miR-206/RAB22A Axis
Yu Gao1, Jianwei Yue2, Zhiliang Huang3
1Department of Geriatrics, The Sixth Hospital of Wuhan, Wuhan, Hubei, China.
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.
Insights
Long non-coding RNA MIAT promotes atherosclerosis by damaging endothelial cells. MIAT knockdown protects against this injury by regulating the miR-206/RAB22A pathway, offering a potential therapeutic target for atherosclerosis.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- RNA Biology
Background:
- Long non-coding RNA myocardial infarction associated transcript (MIAT) plays a role in atherosclerosis (AS).
- The specific functions of MIAT in endothelial cell dysfunction remain unclear.
Purpose of the Study:
- To investigate the role of MIAT in endothelial cell dysfunction induced by oxidized low-density lipoprotein (ox-LDL).
- To elucidate the molecular mechanism involving microRNA-206 (miR-206) and Ras-related protein Rab-22A (RAB22A).
Main Methods:
- Quantitative real-time polymerase chain reaction and western blot to assess gene and protein expression.
- Cellular assays (viability, invasion, migration, apoptosis, EMT) to evaluate endothelial cell injury.
- Dual-luciferase reporter and RNA immunoprecipitation assays to confirm molecular interactions.
Main Results:
- MIAT expression was elevated in ox-LDL-treated human umbilical vein endothelial cells (HUVECs).
- MIAT knockdown improved HUVEC viability, migration, invasion, and epithelial-mesenchymal transition (EMT) while reducing apoptosis and inflammation.
- MIAT directly targeted miR-206, which in turn targeted RAB22A, establishing a regulatory axis.
Conclusions:
- MIAT knockdown mitigates ox-LDL-induced HUVEC injury through the miR-206/RAB22A pathway.
- This finding highlights MIAT's potential as a therapeutic target for atherosclerosis.
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