Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells.
Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells.
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DOI：
10.1186/1743-422x-7-271
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发表时间：
2010-10-15
期刊：
影响因子：
4.8
通讯作者：
Busson P
中科院分区：
文献类型：
--
作者：
Gourzones C;Gelin A;Bombik I;Klibi J;Vérillaud B;Guigay J;Lang P;Témam S;Schneider V;Amiel C;Baconnais S;Jimenez AS;Busson P
鼻咽癌（NPC）是一种与eb病毒相关的人类上皮恶性肿瘤。病毒基因组包含在所有恶性细胞的细胞核中，具有大量转录的病毒microrna家族，称为BART miRNAs。MicroRNAs是众所周知的基因表达的细胞内调控元件。此外，它们经常在细胞外空间输出，有时在不同于产生细胞的受体细胞中转移。microrna的细胞外运输通过多种过程得到促进，包括与保护性蛋白的结合和外泌体中分泌的纳米囊泡的包装。恶性细胞产生的microRNAS存在于肿瘤患者的血液和唾液中，特别是被诊断为胶质母细胞瘤或卵巢癌的患者。在此背景下，我们决定研究鼻咽癌细胞对BART mirna的细胞外释放，以及在鼻咽癌患者血液中检测到它们的可能性。为了解决这个问题，我们通过定量RT-PCR研究了鼻咽癌细胞在体外释放的外泌体以及移植鼻咽癌裸鼠和鼻咽癌患者的血浆样本中BART家族的5个microrna的状态。我们报道BART mirna在细胞外空间被NPC细胞释放，至少在很大程度上与分泌的外泌体相关。它们在鼻咽癌移植裸鼠和鼻咽癌患者的血浆样品中具有良好的选择性。体外和体内鼻咽癌细胞分泌病毒BART mirna。它们有足够的稳定性从肿瘤部位扩散到外周血。该研究为探索它们作为新型肿瘤生物标志物的潜力及其在恶性和非恶性细胞之间的通讯中的可能作用提供了基础。
Nasopharyngeal carcinoma (NPC) is a human epithelial malignancy consistently associated with the Epstein-Barr virus. The viral genome is contained in the nuclei of all malignant cells with abundant transcription of a family of viral microRNAs called BART miRNAs. MicroRNAs are well known intra-cellular regulatory elements of gene expression. In addition, they are often exported in the extra-cellular space and sometimes transferred in recipient cells distinct from the producer cells. Extra-cellular transport of the microRNAs is facilitated by various processes including association with protective proteins and packaging in secreted nanovesicles called exosomes. Presence of microRNAS produced by malignant cells has been reported in the blood and saliva of tumor-bearing patients, especially patients diagnosed with glioblastoma or ovarian carcinoma. In this context, it was decided to investigate extra-cellular release of BART miRNAs by NPC cells and their possible detection in the blood of NPC patients. To address this question, we investigated by quantitative RT-PCR the status of 5 microRNAs from the BART family in exosomes released by NPC cells in vitro as well as in plasma samples from NPC xenografted nude mice and NPC patients. We report that the BART miRNAs are released in the extra-cellular space by NPC cells being associated, at least to a large extent, with secreted exosomes. They are detected with a good selectivity in plasma samples from NPC xenografted nude mice as well as NPC patients. Viral BART miRNAs are secreted by NPC cells in vitro and in vivo. They have enough stability to diffuse from the tumor site to the peripheral blood. This study provides a basis to explore their potential as a source of novel tumor biomarkers and their possible role in communications between malignant and non-malignant cells.