Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10.
Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10.
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来自鼻咽癌来源的外泌体的转移相关 miR-23a 通过抑制新靶基因 TSGA10 介导血管生成
DOI：
10.1038/s41388-018-0183-6
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发表时间：
2018-05
期刊：
影响因子：
8
通讯作者：
You Y
中科院分区：
文献类型：
--
作者：
Bao L;You B;Shi S;Shan Y;Zhang Q;Yue H;Zhang J;Zhang W;Shi Y;Liu Y;Wang X;Liu D;You Y
受益于更精确的成像和放射治疗，局部鼻咽癌（NPC）患者的生存率显着提高。尽管如此，远处转移仍然是主要的失败模式。癌症研究的进展已经强调病理性血管生成是肿瘤转移所必需的，其通过提供氧气、营养物或细胞转移管道。microRNAs（miRNAs）是一类小分子非编码RNA，在生理和病理条件下参与调控血管生成。目前，我们检测到miR-23 a在转移或转移前阶段的NPC组织中高度富集，并且其在NPC中的水平与微血管密度相关。随后，我们证明了miR-23 a表达的改变调节体外HUVECs的生长、迁移和管形成，并影响斑马鱼模型中的血管生长。考虑到细胞外miR-23 a从CNE 2细胞水平转移到HUVECs的可能性，我们分析了包裹在外泌体中的miR-23 a，表明外泌体miR-23 a在NPC中的过表达促进了体外和体内的血管生成。此外，我们提供的证据表明，miR-23 a调节血管生成通过直接靶向睾丸特异性基因抗原（TSGA 10）。综上所述，我们的研究结果表明，来自NPC来源的外泌体的转移相关miR-23 a通过靶向TSGA 10在介导血管生成中起重要作用。
Benefiting from more precise imaging and radiotherapy, patients with locoregionally nasopharyngeal carcinoma (NPC) have a significantly higher survival rate. Nonetheless, distant metastasis is still the predominant mode of failure. Advances in cancer research have highlighted that pathological angiogenesis is necessary for tumor metastasis by offering oxygen, nutrients, or cell metastatic conduits. MicroRNAs (miRNAs), a class of small noncoding RNAs, are increasingly implicated in modulation of angiogenesis in physiological and pathological conditions. Currently, we detected that miR-23a was highly enriched in NPC tissues at the metastatic or premetastatic stage, and its levels in NPC were associated with microvessel density. Subsequently, we proved that alteration of miR-23a expression modulated the growth, migration, and tube formation of HUVECs in vitro and affected the blood vessel outgrowth in the zebrafish model. Considering the possibility that extracellular miR-23a was horizontally transferred from CNE2 cells to HUVECs, we analyzed miR-23a encapsulated in exosomes, showing that overexpression of exosomal miR-23a in NPC promoted angiogenesis both in vitro and in vivo. Moreover, we provided evidences that miR-23a regulated angiogenesis by directly targeting testis-specific gene antigen (TSGA10). Taken together, our findings revealed that metastasis-associated miR-23a from NPC-derived exosomes plays an important role in mediating angiogenesis by targeting TSGA10.
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DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
64.5
作者：
Eulalio, Ana;Huntzinger, Eric;Izaurralde, Elisa
通讯作者：
Izaurralde, Elisa
影响因子：
11.2
作者：
Hatzl S;Geiger O;Kuepper MK;Caraffini V;Seime T;Furlan T;Nussbaumer E;Wieser R;Pichler M;Scheideler M;Nowek K;Jongen-Lavrencic M;Quehenberger F;Wölfler A;Troppmair J;Sill H;Zebisch A
通讯作者：
Zebisch A
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
45.3
作者：
Langendijk, JA;Leemans, CR;Slotman, BJ
通讯作者：
Slotman, BJ