Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Via Tronto 10/a, 60020, Ancona, Italy.
Department of Clinical and Molecular Sciences, Section of Occupational Medicine, Via Tronto 10/a, 60020, Ancona, Italy.
Sci Rep. 2017 Nov 10;7(1):15277. doi: 10.1038/s41598-017-15475-6.
Lung cancer is one of the leading causes of cancer-related deaths. It is diagnosed mostly at the locally advanced or metastatic stage. Recently, micro RNAs (miRs) and their distribution in circulation have been implicated in physiological and pathological processes. In this study, miR-126 was evaluated in serum, exosome and exosome-free serum fractions in non-small cell lung cancer (NSCLC) patients at early and advanced stages, and compared with healthy controls. Down-regulation of miR-126 was found in serum of advanced stage NSCLC patients. In healthy controls, circulating miR-126 was equally distributed between exosomes and exosome-free serum fractions. Conversely, in both early and advanced stage NSCLC patients, miR-126 was mainly present in exosomes. Different fractions of miR-126 in circulation may reflect different conditions during tumour formation. Incubation of exosomes from early and advanced NSCLC patients induced blood vessel formation and malignant transformation in human bronchial epithelial cells. On the other hand, exosome-enriched miR-126 from normal endothelial cells inhibited cell growth and induces loss of malignancy of NSCLC cells. These findings suggest a role of exo-miRs in the modulation of the NSCLC microenvironmental niche. Exosome-delivered miRs thus hold a substantial promise as a diagnostics biomarker as well as a personalized therapeutic modality.
肺癌是癌症相关死亡的主要原因之一。它主要在局部晚期或转移性阶段被诊断出来。最近，微小 RNA（miRs）及其在循环中的分布与生理和病理过程有关。在这项研究中，评估了非小细胞肺癌（NSCLC）患者早期和晚期血清、外泌体和无外泌体血清部分中的 miR-126，并与健康对照组进行了比较。发现晚期 NSCLC 患者血清中 miR-126 下调。在健康对照组中，循环 miR-126 在 exosomes 和无 exosome 的血清部分之间均匀分布。相反，在早期和晚期 NSCLC 患者中，miR-126 主要存在于 exosomes 中。循环中不同的 miR-126 部分可能反映了肿瘤形成过程中的不同情况。来自早期和晚期 NSCLC 患者的 exosomes 孵育诱导人支气管上皮细胞血管形成和恶性转化。另一方面，来自正常内皮细胞的富含外泌体的 miR-126 抑制 NSCLC 细胞的生长并诱导其失去恶性。这些发现表明外泌体 miR 在调节 NSCLC 微环境龛位中起作用。因此，外泌体递送的 miR 作为诊断生物标志物以及个性化治疗方式具有很大的潜力。
