Extracellular RNA transfer from non-malignant human cholangiocytes can promote cholangiocarcinoma growth.
Extracellular RNA transfer from non-malignant human cholangiocytes can promote cholangiocarcinoma growth.
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DOI：
10.1002/2211-5463.13294
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发表时间：
2021-12
期刊：
影响因子：
2.6
通讯作者：
Haneda M
中科院分区：
文献类型：
--
作者：
Ota Y;Takahashi K;Otake S;Tamaki Y;Okada M;Yan I;Aso K;Fujii S;Patel T;Haneda M
细胞分泌组中的细胞外囊泡（EV）通过其将供体来源的RNA转移到受体细胞中的能力而成为肿瘤生长中涉及的病理过程的调节剂。虽然已经研究了肿瘤微环境中肿瘤和基质细胞EV的影响，但对正常非转化细胞的贡献知之甚少。我们研究了来自非恶性细胞的细胞分泌组内的EV对胆管癌细胞中转化细胞生长和行为的影响。这些作用在促纤维化介质TGF-β的存在下增强。我们鉴定了miR-195作为正常细胞中的TGF-β响应性miRNA，其可以通过EV转移到肿瘤细胞并调节细胞生长、侵袭和迁移。miR-195的作用涉及通过直接作用于转录因子Snail来调节上皮-间充质转化。这些研究为正常细胞分泌组对转化细胞生长的影响提供了体外和体内证据，显示了EV RNA转移的重要性，并确定了EV介导的miRNA转移机制作为肿瘤发展的贡献者，这可能为靶向人类胆管癌提供新的治疗机会。胆管细胞分泌组可以包括含有肿瘤抑制性非编码RNA（如miR-195）的细胞外囊泡（EV），并有助于胆管癌生长的微环境调节。miR-195可以抑制上皮-间质转化，抑制肿瘤的侵袭、迁移和生长。
Extracellular vesicles (EV) within the cellular secretome are emerging as modulators of pathological processes involved in tumor growth through their ability to transfer donor‐derived RNA into recipient cells. While the effects of tumor and stromal cell EVs within the tumor microenvironment have been studied, less is known about the contributions of normal, nontransformed cells. We examined the impact of EVs within the cellular secretome from nonmalignant cells on transformed cell growth and behavior in cholangiocarcinoma cells. These effects were enhanced in the presence of the pro‐fibrogenic mediator TGF‐β. We identified miR‐195 as a TGF‐β responsive miRNA in normal cells that can be transferred via EV to tumor cells and regulate cell growth, invasion, and migration. The effects of miR‐195 involve modulation of the epithelial–mesenchymal transition through direct effects on the transcription factor Snail. These studies provide in vitro and in vivo evidence for the impact of normal cellular secretome on transformed cell growth, show the importance of EV RNA transfer, and identify mechanisms of EV‐mediated transfer of miRNA as a contributor to tumor development, which may provide new therapeutic opportunities for targeting human cholangiocarcinoma. Cholangiocyte cell secretome can include extracellular vesicles (EV) containing tumor‐suppressive noncoding RNA such as miR‐195 and contribute to microenvironmental modulation of cholangiocarcinoma growth. miR‐195 can suppress the epithelial–mesenchymal transition and inhibit tumor invasion, migration, and growth.
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影响因子：
--
作者：
Ota Y;Takahashi K;Otake S;Tamaki Y;Okada M;Aso K;Makino Y;Fujii S;Ota T;Haneda M
通讯作者：
Haneda M
影响因子：
11.2
作者：
Gao D;Vahdat LT;Wong S;Chang JC;Mittal V
通讯作者：
Mittal V
影响因子：
3
作者：
Khori, Vahid;Alizadeh, Ali Mohammad;Khodayari, Hamid
通讯作者：
Khodayari, Hamid
影响因子：
50.3
作者：
Becker A;Thakur BK;Weiss JM;Kim HS;Peinado H;Lyden D
通讯作者：
Lyden D
细胞间纳米层介导的microRNA转移：肝癌细胞生长的环境调节机制。
影响因子：
13.5
作者：
Kogure, Takayuki;Lin, Wen-Lang;Yan, Irene K.;Braconi, Chiara;Patel, Tushar
通讯作者：
Patel, Tushar