首页|miR-802靶向调控PI3K/Akt信号通路促进肝细胞癌血管新生的机制研究

miR-802靶向调控PI3K/Akt信号通路促进肝细胞癌血管新生的机制研究

Mechanism of miR-802 targeting PI3K/Akt signaling pathway in promoting angiogenesis of hepatocellular carcinoma

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目的 探究miR-802 在肝细胞癌(HCC)细胞中的表达及其对肿瘤血管新生的影响及作用机制.方法 通过转染miR-802 agomir、miR-802 antagomir上调或抑制人HCC细胞系SMMC-7721 中miR-802 的表达水平.将SMMC-7721 细胞分为NC组(正常培养细胞)、miR-802 agomir组(转染miR-802 agomir)和miR-802 antagomir组(转染miR-802 antagomir).采用小管形成实验和Transwell实验检测过表达miR-802 的SMMC-7721 细胞上清液对人脐静脉内皮细胞(HUVEC)成管能力及迁移能力的影响.采用蛋白质印迹法检测miR-802 agomir组中磷脂酰肌醇 3 激酶(PI3K)、磷酸化PI3K(p-PI3K)、蛋白激酶B(Akt)、磷酸化Akt(p-Akt)、血管内皮生长因子(VEGF)的表达水平.采用免疫荧光实验检测过表达miR-802 对VEGF生成的影响.结果 与NC组相比,miR-802 agomir组HUVEC细胞的成管能力及迁移能力均显著增强,miR-802 antagomir组HUVEC细胞的成管能力及迁移能力均显著降低,差异均有统计学意义(P均<0.05).与NC组相比,miR-802 agomir组SMMC-7721 细胞中VEGF生成量增加,p-PI3K、p-Akt、Akt蛋白表达水平均显著升高,差异均有统计学意义(P均<0.05).结论 miR-802 可通过调控PI3K/Akt信号通路促进VEGF的释放,参与血管新生,从而促进HCC的发生和进展.
Objective This paper attempts to investigate the expression of miR-802 in hepatocellular carcinoma cells and its effect on tumor angiogenesis and mechanism of action.Methods The expression of miR-802 in human hepatocellular carcinoma cell line SMMC-7721 was up-regulated or inhibited by transfection of miR-802 agomir and miR-802 antagomir.SMMC-7721 cells were divided into the NC group(normal cultured cells),the miR-802 agomir group(transfected with miR-802 agomir),and the miR-802 antagomir group(transfected with miR-802 antagomir).The effects of SMMC-7721 cell supernatant overexpressing miR-802 on the tube-forming and migratory abilities of human umbilical vein endothelial cells(HUVEC)were detected by using tubule formation assay and Transwell assay.The expression of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and vascular endothelial growth factor(VEGF)was detected by western blotting in the miR-802 agomir group.Immunofluorescence assay was used to detect the effect of overexpression of miR-802 on VEGF production.Results Compared with the NC group,the tube-forming and migratory abilities of HUVEC cells in the miR-802 agomir group are enhanced,and the tube-forming and migratory abilities of HUVEC cells in the miR-802 antagomir group are reduced,with statistically significant differences(P<0.05).Compared with the NC group,the production of VEGF of SMMC-7721 cells in the miR-802 agomir group is increased,and the protein expression of p-PI3K,p-Akt,and Akt is elevated,with statistically significant differences(P<0.05).Conclusion miR-802 can promote the release of VEGF through regulating the PI3K/Akt signaling pathway,and then participate in angiogenesis,thus promoting the occurrence and progression of hepatocellular carcinoma.

Hepatocellular carcinomamiR-802AngiogenesisPI3K/Akt signaling pathway

刘文豪、倪敏、沈甫明、金涌

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230032 安徽合肥,安徽医科大学药学院

200072 上海,同济大学附属第十人民医院临床药学部

肝细胞癌 miR-802 血管新生 PI3K/Akt信号通路

上海市崇明区可持续发展科技创新行动计划

CKY2022-24

2024

国际消化病杂志
上海市医学科学技术情报研究所

国际消化病杂志

CSTPCD
影响因子:0.796
ISSN:1673-534X
年,卷(期):2024.44(1)
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