癌细胞衍生的外泌体通过 miR-199b-5p/HIF1AN 轴促进 NSCLC 的进展。

Cancer cell-derived exosomes promote NSCLC progression via the miR-199b-5p/HIF1AN axis.

机构信息

Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250000, China; The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Department of Respiratory Medicine, Wuhu Hospital, East China Normal University (The People's Second Hospital of Wuhu), Wuhu, Anhui, 241000, China.

Department of Respiration and Critical Care Medicine, Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Clinical Research Center for Respiratory Disease in Anhui Province, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China.

出版信息

Mol Immunol. 2024 Oct;174:32-40. doi: 10.1016/j.molimm.2024.08.001. Epub 2024 Aug 17.

DOI:10.1016/j.molimm.2024.08.001

PMID:39154583

Abstract

BACKGROUND

Exosomes are mediators of intercellular communication. Cancer cell-secreted exosomes allow exosome donor cells to promote cancer growth, as well as metastasis.

METHODS

Here, exosomes were isolated from the serum of non-small cell lung cancer (NSCLC) patients and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blot analysis. NSCLC cell proliferation and migration were assessed using CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assays. H1299 tumor formation and pulmonary metastasis were examined in a xenograft model in nude mice.

RESULTS

We found that exosomes derived from NSCLC (NSCLC-Exos) promoted NSCLC cell migration and proliferation, and that NSCLC-Exo-mediated malignant progression of NSCLC was mediated by miR-199b-5p. Inhibition of miR-199b-5p decreased the effects of NSCLC-Exos on NSCLC malignant progression. HIF1AN was identified as a downstream target of miR-199b-5p. Furthermore, overexpression of HIF1AN reversed the effects of miR-199b-5p on NSCLC malignant progression.

CONCLUSION

In summary, our findings demonstrated that exosomal-specific miR-199b-5p promoted proliferation in distant or neighboring cells via the miR-199b-5p/HIF1AN axis, resulting in enhanced tumor growth.

摘要

背景

外泌体是细胞间通讯的介质。癌细胞分泌的外泌体使外泌体供体细胞能够促进癌症生长和转移。

方法

在这里，我们从非小细胞肺癌（NSCLC）患者的血清中分离出外泌体，并通过透射电子显微镜（TEM）、纳米颗粒跟踪分析（NTA）和 Western blot 分析对其进行了表征。使用 CCK-8、5-乙炔基-2'-脱氧尿苷（EdU）和 Transwell 测定法评估了 NSCLC 细胞的增殖和迁移。在裸鼠异种移植模型中检查了 H1299 肿瘤形成和肺转移。

结果

我们发现源自 NSCLC（NSCLC-Exos）的外泌体促进了 NSCLC 细胞的迁移和增殖，并且 NSCLC-Exo 介导的 NSCLC 恶性进展是由 miR-199b-5p 介导的。抑制 miR-199b-5p 降低了 NSCLC-Exos 对 NSCLC 恶性进展的影响。HIF1AN 被鉴定为 miR-199b-5p 的下游靶标。此外，HIF1AN 的过表达逆转了 miR-199b-5p 对 NSCLC 恶性进展的影响。