Victor Chang Cardiac Research Institute; Sydney, Australia.
RNA Biol. 2013 Aug;10(8):1333-44. doi: 10.4161/rna.25281. Epub 2013 Jun 17.
Interactions between glioma cells and their local environment are critical determinants of brain tumor growth, infiltration and neovascularisation. Communication with host cells and stroma via microvesicles represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. Here we have taken an unbiased approach to identifying RNAs in glioma-derived microvesicles, and explored their potential to regulate gene expression in recipient cells. We find that glioma microvesicles are predominantly of exosomal origin and contain complex populations of coding and noncoding RNAs in proportions that are distinct from those in the cells from which they are derived. Microvesicles show a relative depletion in microRNA compared with their cells of origin, and are enriched in unusual or novel noncoding RNAs, most of which have no known function. Short-term exposure of brain microvascular endothelial cells to glioma microvesicles results in many gene expression changes in the endothelial cells, most of which cannot be explained by direct delivery of transcripts. Our data suggest that the scope of potential actions of tumor-derived microvesicles is much broader and more complex than previously supposed, and highlight a number of new classes of small RNA that remain to be characterized.
胶质母细胞瘤细胞与其局部环境的相互作用是决定脑肿瘤生长、浸润和新生血管形成的关键因素。通过微泡与宿主细胞和基质进行通讯是肿瘤改变其周围环境以实现肿瘤允许的环境的途径之一。在这里，我们采用了一种无偏见的方法来鉴定源自神经胶质瘤的微泡中的 RNA，并探索了它们在受体细胞中调节基因表达的潜力。我们发现，神经胶质瘤微泡主要来源于外泌体，并且含有编码和非编码 RNA 的复杂群体，其比例与它们起源的细胞不同。与起源细胞相比，微泡中的 microRNA 相对较少，并且富含不常见或新颖的非编码 RNA，其中大多数没有已知的功能。脑微血管内皮细胞短期暴露于神经胶质瘤微泡会导致内皮细胞中许多基因表达发生变化，其中大多数变化不能用转录本的直接传递来解释。我们的数据表明，肿瘤衍生的微泡的潜在作用范围比以前想象的要广泛和复杂得多，并强调了许多仍有待表征的新的小 RNA 类别。
