{"title":"DDX5 通过 miR-640/SOX6 轴在氧化-LDL 诱导的内皮细胞损伤中的调控机制","authors":"Shuo Li, Yu Wang","doi":"10.3233/CH-242254","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Endothelial dysfunction is an early and pre-clinical manifestation of coronary heart disease (CHD).</p><p><strong>Objective: </strong>This study investigates the role of DDX5 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury to confer novel targets for the treatment of CHD.</p><p><strong>Methods: </strong>Endothelial cells were induced by ox-LDL. DDX5, pri-miR-640, pre-miR-640, miR-640, and SOX6 expressions were analyzed by RT-qPCR and Western blot. DDX5 expression was intervened by shRNA, followed by CCK-8 analysis of proliferation, flow cytometry detection of apoptosis, and tube formation assay analysis of angiogenic potential of cells. The binding between DDX5 and pri-miR-640 was determined by RIP, and the pri-miR-640 RNA stability was measured after actinomycin D treatment. Dual-luciferase assay verified the targeting relationship between miR-640 and SOX6.</p><p><strong>Results: </strong>DDX5 and miR-640 were highly expressed while SOX6 was poorly expressed in ox-LDL-induced endothelial cells. Silence of DDX5 augmented cell proliferation, abated apoptosis, and facilitated angiogenesis. Mechanistically, RNA binding protein DDX5 elevated miR-640 expression by weakening the degradation of pri-miR-640, thereby reducing SOX6 expression. Combined experimental results indicated that overexpression of miR-640 or low expression of SOX6 offset the protective effect of DDX5 silencing on cell injury.</p><p><strong>Conclusion: </strong>DDX5 elevates miR-640 expression by repressing the degradation of pri-miR-640 and then reduces SOX6 expression, thus exacerbating ox-LDL-induced endothelial cell injury.</p>","PeriodicalId":93943,"journal":{"name":"Clinical hemorheology and microcirculation","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Regulatory mechanism of DDX5 in ox-LDL-induced endothelial cell injury through the miR-640/SOX6 axis.\",\"authors\":\"Shuo Li, Yu Wang\",\"doi\":\"10.3233/CH-242254\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Endothelial dysfunction is an early and pre-clinical manifestation of coronary heart disease (CHD).</p><p><strong>Objective: </strong>This study investigates the role of DDX5 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury to confer novel targets for the treatment of CHD.</p><p><strong>Methods: </strong>Endothelial cells were induced by ox-LDL. DDX5, pri-miR-640, pre-miR-640, miR-640, and SOX6 expressions were analyzed by RT-qPCR and Western blot. DDX5 expression was intervened by shRNA, followed by CCK-8 analysis of proliferation, flow cytometry detection of apoptosis, and tube formation assay analysis of angiogenic potential of cells. The binding between DDX5 and pri-miR-640 was determined by RIP, and the pri-miR-640 RNA stability was measured after actinomycin D treatment. Dual-luciferase assay verified the targeting relationship between miR-640 and SOX6.</p><p><strong>Results: </strong>DDX5 and miR-640 were highly expressed while SOX6 was poorly expressed in ox-LDL-induced endothelial cells. Silence of DDX5 augmented cell proliferation, abated apoptosis, and facilitated angiogenesis. Mechanistically, RNA binding protein DDX5 elevated miR-640 expression by weakening the degradation of pri-miR-640, thereby reducing SOX6 expression. Combined experimental results indicated that overexpression of miR-640 or low expression of SOX6 offset the protective effect of DDX5 silencing on cell injury.</p><p><strong>Conclusion: </strong>DDX5 elevates miR-640 expression by repressing the degradation of pri-miR-640 and then reduces SOX6 expression, thus exacerbating ox-LDL-induced endothelial cell injury.</p>\",\"PeriodicalId\":93943,\"journal\":{\"name\":\"Clinical hemorheology and microcirculation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical hemorheology and microcirculation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3233/CH-242254\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical hemorheology and microcirculation","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3233/CH-242254","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Regulatory mechanism of DDX5 in ox-LDL-induced endothelial cell injury through the miR-640/SOX6 axis.
Background: Endothelial dysfunction is an early and pre-clinical manifestation of coronary heart disease (CHD).
Objective: This study investigates the role of DDX5 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury to confer novel targets for the treatment of CHD.
Methods: Endothelial cells were induced by ox-LDL. DDX5, pri-miR-640, pre-miR-640, miR-640, and SOX6 expressions were analyzed by RT-qPCR and Western blot. DDX5 expression was intervened by shRNA, followed by CCK-8 analysis of proliferation, flow cytometry detection of apoptosis, and tube formation assay analysis of angiogenic potential of cells. The binding between DDX5 and pri-miR-640 was determined by RIP, and the pri-miR-640 RNA stability was measured after actinomycin D treatment. Dual-luciferase assay verified the targeting relationship between miR-640 and SOX6.
Results: DDX5 and miR-640 were highly expressed while SOX6 was poorly expressed in ox-LDL-induced endothelial cells. Silence of DDX5 augmented cell proliferation, abated apoptosis, and facilitated angiogenesis. Mechanistically, RNA binding protein DDX5 elevated miR-640 expression by weakening the degradation of pri-miR-640, thereby reducing SOX6 expression. Combined experimental results indicated that overexpression of miR-640 or low expression of SOX6 offset the protective effect of DDX5 silencing on cell injury.
Conclusion: DDX5 elevates miR-640 expression by repressing the degradation of pri-miR-640 and then reduces SOX6 expression, thus exacerbating ox-LDL-induced endothelial cell injury.
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