Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma.
Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma.
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DOI：
10.1002/hep.29586
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Selaru FM
中科院分区：
文献类型：
--
作者：
Wang F;Li L;Piontek K;Sakaguchi M;Selaru FM
肝细胞癌（HCC）是一种常见的致命癌症。大多数HCC病例发生在硬化/纤维化肝脏中，这增加了环境在癌症发生中起重要作用的可能性。我们小组和其他人以前的研究表明，在促结缔组织增生性癌症中，活化的癌症相关成纤维细胞（CAF）和癌细胞之间存在丰富的细胞间通讯。此外，细胞外囊泡（EV）或外泌体被确定为这种细胞间通讯平台的重要分支。最后，这些研究表明EV可以在体内携带miR物质并将其递送至促结缔组织增生性癌症。活化的肝成纤维细胞/星状细胞在HCC发展中所起的确切作用还不清楚。根据之前的研究，激活的成纤维细胞产生由EV携带的促进HCC发生的信号似乎是合理的。在目前的研究中，我们首先假设，然后表明，星状细胞衍生的EV 1）可以加载有选择的miR种类（miR-335- 5 p）; 2）在体外并且更重要地在体内被HCC细胞摄取; 3）可以在体外以及体内将miR-335- 5 p货物供应给受体HCC细胞;最后，它们4）在体外抑制HCC细胞增殖和侵袭以及在体内诱导HCC肿瘤缩小。最后，我们鉴定了在用EV-miR-335- 5 p处理后下调的miR-335的mRNA靶标。这项研究为HCC提供了新的治疗策略，其中星状细胞衍生的EV装载有治疗性核酸并在体内递送。
Hepatocellular Cancer (HCC) is a common and deadly cancer. Most cases of HCC arise in a cirrhotic/fibrotic liver, raising the possibility that the environment plays a paramount role in cancer genesis. Previous studies from our group and others have shown that, in desmoplastic cancers, there is a rich intercellular communication between activated, cancer-associated fibroblasts (CAF) and cancer cells. Moreover, Extracellular Vesicles (EVs), or exosomes, were identified as an important arm of this intercellular communication platform. Last, these studies have shown that EVs can carry miR species in vivo and deliver them to desmoplastic cancers. The precise role played by activated liver fibroblasts/stellate cells in HCC development is insufficiently known. Based on previous studies, it appears plausible that activated fibroblasts produce signals carried by EVs that promote HCC genesis. In the current study, we first hypothesized and then showed that stellate cell-derived EVs 1) can be loaded with a miR species of choice (miR-335-5p); 2) are uptaken by HCC cells in vitro and more importantly in vivo; 3) can supply the miR-335-5p cargo to recipient HCC cells in vitro as well as in vivo; and finally that they 4) inhibit HCC cell proliferation and invasion in vitro as well as induce HCC tumor shrinkage in vivo. Last, we identified mRNA targets for miR-335 that are down-regulated following treatments with EV-miR-335-5p. This study informs novel therapeutic strategies in HCC, whereby stellate cell-derived EVs are loaded with therapeutic nucleic acids and delivered in vivo.
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影响因子：
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发表时间：
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影响因子：
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作者：
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发表时间：
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