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Bone mesenchymal stem cells derived extracellular vesicles promotes TRAIL-related apoptosis of hepatocellular carcinoma cells via the delivery of microRNA-20a-3p.

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机构: [1]National Engineering Research Center for Biomaterials, Engineering Research Center in Biomaterials, Sichuan University, Chengdu, Sichuan, China [2]College of Computer Science, Chengdu Normal University, Chengdu, Sichuan, China [3]Antibiotic Drug Office, Sichuan Institute of Veterinary Drug Control, Chengdu, Sichuan, China [4]Orthopedics Department, Chengdu First People’s Hospital, Chengdu, Sichuan, China
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关键词: Hepatocellular carcinoma extracellular vesicles bone mesenchymal stem cells miR-20a-39 c-FLIP TRAIL

摘要:
Bone mesenchymal stem cells (BMSCs) have been widely researched in cancer treatment, including hepatocellular carcinoma (HCC). This study intended to discuss the mechanism of miR-20a-3p in BMSCs-extracellular vesicles (EVs) in HCC apoptosis. BMSCs were isolated and identified. EVs derived from BMSCs were extracted and identified. After overexpressing or inhibiting miR-20a-3p expression in BMSCs, EVs were extracted and acted on HCC cells and transplanted tumors. HCC cell apoptosis in the treatment of BMSCs-conditioned medium, BMSCs-EVs and/or miR-20a-3p mimic/inhibitor were evaluated, with the detection of levels of TRAIL and TRAIL-related proteins. A functional rescue experiment about c-FLIP was carried out in HCC cells. The target binding relationship between miR-20a-3p and c-FLIP was detected. The subcutaneous tumorigenesis model of mice was established and injected with BMSCs-EVs to estimate the effect of BMSCs-EVs-miR-20a-3p on HCC growth. EVs isolated from BMSCs conditioned medium promoted the apoptosis of HCC cells. After BMSCs-EVs treatment, TRAIL levels, downstream proteins and miR-20a-3p were increased significantly, but the expression of c-FLIP was decreased. miR-20a-3p could target c-FLIP. BMSCs-EVs inhibited the growth of HCC cells, decreased c-FLIP expression, increased TRAIL levels, and promote the of HCC cell apoptosis. BMSCs-EVs with overexpressing miR-20a-3p further enhanced the apoptotic effect of HCC cells in vitro and in vivo. BMSCs-EVs-carried miR-20a-3p targets c-FLIP and increases TRAIL levels in HCC cells, thus promoting TRAIL-related apoptosis.

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出版当年[2021]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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第一作者机构: [1]National Engineering Research Center for Biomaterials, Engineering Research Center in Biomaterials, Sichuan University, Chengdu, Sichuan, China [*1]National Engineering Research Center for Biomaterials, Engineering Research Center in Biomaterials, Sichuan University, No. 29 Wangjiang Road, Chengdu, Sichuan 610064, China.
通讯作者:
通讯机构: [1]National Engineering Research Center for Biomaterials, Engineering Research Center in Biomaterials, Sichuan University, Chengdu, Sichuan, China [*1]National Engineering Research Center for Biomaterials, Engineering Research Center in Biomaterials, Sichuan University, No. 29 Wangjiang Road, Chengdu, Sichuan 610064, China.
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