PDF(Pubmed)
Abstract：
Recurrence is one of the major issues in bladder cancer (BCa). Novel technologies, such as the detection of microRNAs carried by extracellular vesicles (EVs) in urine, have been proposed as biomarkers for detecting recurrence in BCa. Although the usefulness of microRNAs in body fluids from cancer patients has been reported, it is also known that they play essential roles in cancer progression. We previously proposed miR-146a-5p as a prognostic marker in BCa, since its urinary expression was associated with grade and tumour depth. However, the specific mechanisms of miR-146a-5p remain unclear. Here, we show the proangiogenic effects of miR-146a-5p secreted by high-grade BCa cells. The urinary miR-146a-5p level was higher in patients with high-grade BCa than in those with low-grade BCa. Similarly, tumours generated by miR-146a-overexpressing BCa cells in mice grew rapidly with high levels of angiogenesis. BCa-derived EV treatment promoted the proliferation of endothelial cells via the inhibition of the demethylase TET2 and the subsequent increase in its downstream target c-Myc. These findings demonstrate that secreted miR-146a-5p contributes to cancer progression by promoting angiogenesis. Therefore, miRNAs in EVs may become not only a diagnostic tool but also a target molecule for therapy.
摘要：
复发是膀胱癌（BCa）的主要问题之一。新技术,例如检测尿液中细胞外囊泡（EV）携带的microRNA，已被提出作为检测BCa复发的生物标志物。尽管已经报道了microRNA在癌症患者体液中的有用性，众所周知，它们在癌症进展中起着至关重要的作用。我们先前提出miR-146a-5p作为BCa的预后标志物，因为它的尿表达与分级和肿瘤深度有关。然而,miR-146a-5p的具体机制尚不清楚.这里,我们显示了由高级BCa细胞分泌的miR-146a-5p的促血管生成作用。高等级BCa患者的尿miR-146a-5p水平高于低等级BCa患者。同样，小鼠中miR-146a过表达的BCa细胞产生的肿瘤随着高水平的血管生成迅速生长。BCa衍生的EV处理通过抑制脱甲基酶TET2并随后增加其下游靶标c-Myc来促进内皮细胞的增殖。这些发现证明分泌的miR-146a-5p通过促进血管生成促进癌症进展。因此,EV中的miRNA可能不仅成为诊断工具，而且成为治疗的靶分子。
