CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20.

IF 3.3 4区医学 Q3 IMMUNOLOGY

Autoimmunity Pub Date : 2025-12-01 Epub Date: 2025-01-25 DOI:10.1080/08916934.2025.2458324

Chen Zheng, Hu Hei, Yifei Zhai, Wenbo Gong, Runfang Zhang, Songtao Zhang

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引用次数: 0

Abstract

Background: Exosomes derived from cancer-associated fibroblasts (CAFs) can affect tumor microenvironment (TME) of thyroid cancer (TC). The cAMP response element binding protein 1 (CREB1) acts as a transcription factor to participate in cancer development. Currently, we aimed to explore the molecular mechanism of exosome-associated CREB1 and C-C motif chemokine ligand 20 (CCL20) in TC.

Methods: The mRNA and protein levels were examined via RT-qPCR and western blot. Gene interaction was analyzed using ChIP and dual-luciferase reporter assays. Cell migration, invasion and proliferation were assessed by wound healing, transwell and EdU assays. Exosomes were characterized by morphology observation and western blot. The proliferation and apoptosis of CD8⁺ T cells were detected by immunofluorescence and flow cytometry. In vivo assays were performed by establishing xenograft models.

Results: CREB1 was highly expressed in TC. CREB1 positively interacted with CCL20 in TC. CREB1 facilitated TC cell migration, invasion and proliferation via targeting CCL20. CCL20 expression was reduced by transferring CAFs-secreted exosomes sheltering CREB1 downregulation. Exosomal CREB1 knockdown receded cell progression and enhanced CD8⁺ T function by mediating CCL20. CAFs-associated exosomal CREB1 downregulation inhibited tumorigenesis through affecting CCL20.

Conclusion: CAFs-derived exosomes accelerated the malignant behaviors and immune evasion in TC by carrying CREB1 to up-regulate CCL20.

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cafs释放的外泌体CREB1通过CCL20的正调控促进甲状腺癌的细胞进展和免疫逃避。

背景：来自癌症相关成纤维细胞（CAFs）的外泌体可以影响甲状腺癌（TC）的肿瘤微环境（TME）。cAMP反应元件结合蛋白1 （CREB1）作为一种转录因子参与癌症的发展。目前，我们的目标是探索外泌体相关CREB1和C-C基序趋化因子配体20 （CCL20）在TC中的分子机制。方法：采用RT-qPCR和western blot方法检测各组大鼠mRNA和蛋白表达水平。采用ChIP和双荧光素酶报告基因法分析基因相互作用。通过伤口愈合、transwell和EdU测定细胞迁移、侵袭和增殖。外泌体通过形态观察和western blot进行表征。采用免疫荧光和流式细胞术检测CD8+ T细胞的增殖和凋亡情况。通过建立异种移植物模型进行体内实验。结果：CREB1在TC中高表达。在TC中，CREB1与CCL20正相互作用。CREB1通过靶向CCL20促进TC细胞迁移、侵袭和增殖。CCL20的表达通过转移cafs分泌的外泌体来保护CREB1下调而降低。外泌体CREB1敲低可通过介导CCL20延缓细胞进展并增强CD8+ T功能。cafs相关外泌体CREB1下调通过影响CCL20抑制肿瘤发生。结论：cafs来源的外泌体通过携带CREB1上调CCL20，加速了TC的恶性行为和免疫逃避。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Autoimmunity 医学-免疫学

CiteScore

5.70

自引率

8.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.