请选择 进入手机版 | 继续访问电脑版
设为首页收藏本站

老西部英语

 找回密码
 立即注册

只需一步,快速开始

[博士论坛]:外泌体- miR-335:一种治疗肝细胞癌的新策略

1

主题

1

资源

18

积分

新手上路

Rank: 1

积分
18
pudding 发表于 2017-11-26 23:29:09 | 显示全部楼层 |阅读模式
本帖最后由 pudding 于 2017-11-26 23:31 编辑


作者: Selaru FM et al                                    
期刊名称:Hepatology
发表时间:2017-10-10
Exosome - miR-335as a novel therapeutic strategy in hepatocellular carcinoma. HepatocellularCancer (HCC) is a common and deadly cancer. Most cases of HCC arise in acirrhotic/fibrotic liver, raising the possibility that the environment plays aparamount role in cancer genesis. Previous studies from our group and othershave shown that, in desmoplastic cancers, there is a rich intercellularcommunication between activated, cancer-associated fibroblasts (CAF) and cancercells. Moreover, Extracellular Vesicles (EVs), or exosomes, were identifiedasan important arm of this intercellular communication platform. Last, thesestudies have shown that EVs can carry miR species in vivo and deliver them todesmoplastic cancers. The precise role played by activated liverfibroblasts/stellate cells in HCC development is insufficiently known. Based onprevious studies, it appears plausible that activated fibroblasts producesignals carried by EVs that promote HCC genesis. In the current study, we firsthypothesized and then showed that stellate cell-derived EVs 1) can be loadedwith a miR species of choice (miR-335-5p); 2) are uptaken by HCC cells in vitroand more importantly in vivo; 3) can supplythe miR-335-5p cargo to recipientHCC cells in vitro as well as in vivo; and finally that they 4) inhibit HCCcell proliferation and invasion in vitroas well as induce HCC tumor shrinkagein vivo. Last, we identified mRNA targets for miR-335 that are down-regulatedfollowing treatments with EV-miR-335-5p. This study informs novel therapeuticstrategies in HCC, whereby stellate cell-derived EVs are loaded withtherapeutic nucleic acids and delivered in vivo.


肝细胞癌(HCC)是一种常见且致命的癌症。大多数HCC病例发生在肝硬化/纤维化的患者身上,这一现象增强了环境在癌症发生中起着最重要作用的可能性。我们之前的研究表明,在结缔组织肿瘤中,活化的肿瘤相关成纤维细胞(CAF)和肿瘤细胞之间存在丰富的细胞间通讯。此外,细胞外囊泡(EVs),或外泌体,已经被确认为是这个细胞间通讯平台的重要组成部分。最后,这些研究表明,细胞外囊泡可以在体内携带微小RNA并将其递送至结缔组织肿瘤。激活的肝成纤维细胞/星状细胞在HCC发展中所起的确切作用尚不清楚。不过,基于先前的研究,激活的成纤维细胞产生促进HCC发生的细胞外膜泡携带的信号这一假设似乎是合理的。在本研究中,我们假设并证明,星状细胞来源的细胞外膜泡具有以下作用:1)可以选择性携带微小RNA(miR-335-5p); 2)在体外被肝癌细胞摄取,更重要的是在体内也可发生这一过程; 3)在体外及体内均可将miR-335-5p呈递给HCC细胞; 4)抑制肝癌细胞的增殖和侵袭,并导致体内肝癌肿瘤缩小。最后,在用EV-miR-335-5p处理后的HCC细胞中,我们鉴定出了下调的miR-335的mRNA靶标。这项研究提供了一种新的肝细胞癌的治疗策略,在这一过程中肝星状细胞来源的细胞外膜泡可携带治疗性的核酸并负责在体内的传递。

博士二教班 牛文博 11700259  


友荐云推荐
评论

使用道具 举报

QQ|关于我们|联系我们|网络条款|建议反馈|小黑屋|老西部英语 ( 版权所有 粤ICP备11103350号  

GMT+8, 2019-8-23 03:57 , Processed in 0.191125 second(s), 36 queries .

Powered by Discuz! X3

© 2001-2013 Comsenz Inc.