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肠型鼻内翻性乳头状腺癌中的 miR-126:miR-126 的外泌体转移促进抗肿瘤反应。

MiR-126 in intestinal-type sinonasal adenocarcinomas: exosomal transfer of MiR-126 promotes anti-tumour responses.

机构信息

Department of Clinical and Molecular Sciences, Section of Occupational Medicine, Polytechnic University of Marche, Via Tronto 10/a, 60020, Ancona, Italy.

International Society of Doctors for the Environment (ISDE), Arezzo, Italy.

出版信息

BMC Cancer. 2018 Sep 17;18(1):896. doi: 10.1186/s12885-018-4801-z.

Abstract

BACKGROUND

Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure. ITACs are generally associated with advanced stage at presentation due to the insidious growth pattern and non-specific symptoms. Therefore, biomarkers that can detect the switch from the benign disease to malignancy are needed. Essential for tumour growth, angiogenesis is an important step in tumour development and progression. This process is strictly regulated, and MiR-126 considered its master modulator.

METHODS

We have investigated MiR-126 levels in ITACs and compared them to benign sinonasal lesions, such as sinonasal-inverted papillomas (SIPs) and inflammatory polyps (NIPs). The tumour-suppressive functions of MiR-126 were also evaluated.

RESULTS

We found that MiR-126 can significantly distinguish malignancy from benign nasal forms. The low levels of MiR-126 in ITACs point to its role in tumour progression. In this context, restoration of MiR-126 induced metabolic changes, and inhibited cell growth and the tumorigenic potential of MNSC cells.

CONCLUSIONS

We report that MiR-126 delivered via exosomes from endothelial cells promotes anti-tumour responses. This paracrine transfer of MiRs may represent a new approach towards MiR-based therapy.

摘要

背景

肠型鼻内翻性乳头状瘤(ITAC)是一种与木尘和皮革暴露有关的侵袭性恶性肿瘤。由于隐匿性生长模式和非特异性症状,ITAC 通常在出现时就处于晚期。因此,需要能够检测从良性疾病向恶性肿瘤转变的生物标志物。血管生成对于肿瘤生长至关重要,是肿瘤发生和发展的重要步骤。这个过程受到严格调控,miR-126 被认为是其主要的调节因子。

方法

我们研究了 ITAC 中的 miR-126 水平,并将其与良性鼻内病变(如鼻内翻性乳头状瘤(SIP)和炎性息肉(NIP))进行了比较。还评估了 miR-126 的肿瘤抑制功能。

结果

我们发现 miR-126 可以显著区分恶性和良性鼻内病变。ITAC 中 miR-126 水平较低表明其在肿瘤进展中的作用。在这种情况下,恢复 miR-126 诱导了代谢变化,并抑制了 MNSC 细胞的生长和致瘤潜能。

结论

我们报告了内皮细胞来源的外泌体中的 miR-126 可促进抗肿瘤反应。这种 miR 的旁分泌转移可能代表了基于 miR 的治疗的一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f147/6142309/a10cc132bd15/12885_2018_4801_Fig1_HTML.jpg

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