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miR-92a-3p promotes ox-LDL induced-apoptosis in HUVECs via targeting SIRT6 and activating MAPK signaling pathway
Xu, Yingchun; Miao, Chunbo; Cui, Jinzhen; Bian, Xiaoli.
  • Xu, Yingchun; The Second Peoples Hospital of Liaocheng. Department of Cardiology. Liaocheng. CN
  • Miao, Chunbo; The Second Peoples Hospital of Liaocheng. Department of Internal Medicine. Liaocheng. CN
  • Cui, Jinzhen; The Second Peoples Hospital of Liaocheng. Department of Internal Medicine. Liaocheng. CN
  • Bian, Xiaoli; Yangzhou Jiangdu Peoples Hospital, Jiangdu District. Department of Cardiology. Yangzhou. CN
Braz. j. med. biol. res ; 54(3): e9386, 2021. graf
Article in English | LILACS | ID: biblio-1153515
ABSTRACT
Atherosclerosis could be induced by multiple factors, including hypertension, hyperlipidemia, and smoking, and its pathogenesis has not been fully elucidated. MicroRNAs have been shown to possess great anti-atherosclerotic potential, but the precise function of miR-92a-3p in atherosclerosis and its potential molecular mechanism have not been well clarified. Flow cytometry assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) assay were performed to evaluate effects of oxidized low-density lipoprotein (ox-LDL) on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs), respectively. Malondialdehyde and superoxide dismutase levels in cell lysate were assessed with biochemical kits. The expression levels of miR-92a-3p and Sirtuin6 (SIRT6) in HUVECs exposed to ox-LDL were estimated by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the protein levels of SIRT6, c-Jun N-terminal kinase (JNK), phosphorylation JNK (p-JNK), p38 mitogen activated protein kinase (p38 MAPK), and phosphorylation p38 MAPK (p-p38 MAPK) were measured by western blot assays. The relationship between miR-92a-3p and SIRT6 was confirmed by dual-luciferase reporter assay. Ox-LDL induced apoptosis and oxidative stress in HUVECs in concentration- and time-dependent manners. Conversely, miR-92a-3p silencing inhibited apoptosis and SIRT6 expression in HUVECs. The overexpression of miR-92a-3p enhanced apoptosis and phosphorylation levels of JNK and p38 MAPK as well as inhibited proliferation in ox-LDL-induced HUVECs. In addition, SIRT6 was a target of miR-92a-3p. miR-92a-3p negatively regulated SIRT6 expression in ox-LDL-induced HUVECs to activate MAPK signaling pathway in vitro. In summary, miR-92a-3p promoted HUVECs apoptosis and suppressed proliferation in ox-LDL-induced HUVECs by targeting SIRT6 expression and activating MAPK signaling pathway.
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Full text: Available Index: LILACS (Americas) Main subject: MAP Kinase Signaling System Limits: Humans Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2021 Type: Article Affiliation country: China Institution/Affiliation country: The Second Peoples Hospital of Liaocheng/CN / Yangzhou Jiangdu Peoples Hospital, Jiangdu District/CN

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Full text: Available Index: LILACS (Americas) Main subject: MAP Kinase Signaling System Limits: Humans Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2021 Type: Article Affiliation country: China Institution/Affiliation country: The Second Peoples Hospital of Liaocheng/CN / Yangzhou Jiangdu Peoples Hospital, Jiangdu District/CN