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

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
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引用次数: 0

摘要

背景外泌体是细胞间通信的媒介。方法从非小细胞肺癌(NSCLC)患者的血清中分离出外泌体,并通过透射电子显微镜(TEM)、纳米颗粒追踪分析(NTA)和免疫印迹分析对其进行表征。使用 CCK-8、5-乙炔基-2′-脱氧尿苷(EdU)和 Transwell 试验评估了 NSCLC 细胞的增殖和迁移。结果我们发现,来自 NSCLC 的外泌体(NSCLC-Exos)促进了 NSCLC 细胞的迁移和增殖,NSCLC-Exo 介导的 NSCLC 恶性进展是由 miR-199b-5p 介导的。抑制 miR-199b-5p 可降低 NSCLC-Exos 对 NSCLC 恶性进展的影响。HIF1AN被确定为miR-199b-5p的下游靶标。总之,我们的研究结果表明,外泌体特异性miR-199b-5p通过miR-199b-5p/HIF1AN轴促进远处或邻近细胞的增殖,导致肿瘤生长增强。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cancer cell-derived exosomes promote NSCLC progression via the miR-199b-5p/HIF1AN axis

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.

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来源期刊
Molecular immunology
Molecular immunology 医学-免疫学
CiteScore
6.90
自引率
2.80%
发文量
324
审稿时长
50 days
期刊介绍: Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.
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