Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1.
Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1.
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缺氧外泌体通过转移长非编码RNA-UCA1促进膀胱肿瘤生长和发育
DOI：
10.1186/s12943-017-0714-8
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发表时间：
2017-08-25
期刊：
影响因子：
37.3
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Xue M;Chen W;Xiang A;Wang R;Chen H;Pan J;Pang H;An H;Wang X;Hou H;Li X
背景为了克服实体瘤的缺氧微环境，肿瘤细胞分泌大量含有非编码RNA的exosomes，促进肿瘤的发生和转移。然而，肿瘤细胞来源的外泌体在缺氧期间的确切机制尚不清楚。在这里，我们的目的是澄清缺氧是否影响肿瘤的生长和进展，通过转移长的非编码RNA尿路上皮癌相关1（lncRNA-UCA 1）丰富的外泌体分泌的膀胱癌celles.MethodsWe使用膀胱癌5637细胞与lncRNA-UCA 1作为外泌体产生细胞和膀胱癌UMUC 2细胞与lncRNA-UCA 1作为受体细胞低表达。通过透射电子显微镜、纳米颗粒跟踪分析和蛋白质印迹分析，分离并鉴定了来源于在常氧或缺氧条件下培养的5637细胞的外泌体。将这些外泌体与UMUC 2细胞共培养以评价细胞增殖、迁移和侵袭。我们通过异种移植模型进一步研究了来源于缺氧5637细胞的外泌体lncRNA-UCA 1的作用。lncRNA-UCA 1在血清来源的外泌体作为膀胱癌的生物标志物的可用性也assessed.ResultsWe发现，来自5637细胞的低氧外泌体促进细胞增殖，迁移和侵袭，和低氧外泌体RNA可以内化由三个膀胱癌细胞系。重要的是，lncRNA-UCA 1在缺氧5637细胞来源的外泌体中分泌。与常氧exosomes相比，来自5637细胞的低氧exosomes显示出更高的lncRNA-UCA 1表达水平。此外，在体外和体内，Hypoproteinexosomal lncRNA-UCA 1可以通过上皮-间质转化促进肿瘤的生长和进展。此外，膀胱癌患者的人血清来源的外泌体中lncRNA-UCA 1的表达水平高于健康对照。我们的研究结果表明，低氧膀胱癌细胞通过分泌致癌lncRNA-UCA 1富集的外泌体和外泌体lncRNA，人血清中UCA 1有可能作为膀胱癌的诊断生物标志物。
BackgroundTo overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells.MethodsWe used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed.ResultsWe found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls.ConclusionTogether, our results demonstrate that hypoxic bladder cancer cells remodel tumor microenvironment to facilitate tumor growth and development though secreting the oncogenic lncRNA-UCA1-enriched exosomes and exosomal lncRNA-UCA1 in human serum has the possibility as a diagnostic biomarker for bladder cancer.
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影响因子：
3.7
作者：
Işın M;Uysaler E;Özgür E;Köseoğlu H;Şanlı Ö;Yücel ÖB;Gezer U;Dalay N
通讯作者：
Dalay N
影响因子：
4.6
作者：
Bian Z;Jin L;Zhang J;Yin Y;Quan C;Hu Y;Feng Y;Liu H;Fei B;Mao Y;Zhou L;Qi X;Huang S;Hua D;Xing C;Huang Z
通讯作者：
Huang Z
影响因子：
50.3
作者：
Jain RK
通讯作者：
Jain RK
外泌体传输的 lncARSR 通过充当竞争性内源性 RNA 促进肾癌舒尼替尼耐药
影响因子：
50.3
作者：
Qu, Le;Ding, Jin;Wang, Lin-Hui
通讯作者：
Wang, Lin-Hui
DOI：
10.1158/1078-0432.ccr-13-3173
发表时间：
2015-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jung HY;Fattet L;Yang J
通讯作者：
Yang J