低氧诱导的肿瘤外泌体通过 miR-1825/TSC2/mTOR 轴促进口腔鳞状细胞癌血管生成。
Hypoxia-induced tumor exosomes promote angiogenesis through miR-1825/TSC2/mTOR axis in oral squamous cell carcinoma.
机构信息
Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum, Turkey.
Molecular Cancer Biology Laboratory, High Technology Application and Research Center, Erzurum Technical University, Erzurum, Turkey.
出版信息
Head Neck. 2023 Sep;45(9):2259-2273. doi: 10.1002/hed.27460. Epub 2023 Jul 14.
BACKGROUND
Oral squamous cell carcinoma (OSCC) is characterized by enhanced angiogenesis resulting in poor prognosis despite improvements in diagnostic/therapeutic techniques. Here, we aimed at investigating potential roles of miR-1825 enclosed in OSCC-derived exosomes on angiogenesis under hypoxic conditions.
METHODS
Effects of miR-1825 mimic/inhibitor as well as hypoxia-induced tumor derived exosomes on human umbilical vein endothelial cells (HUVECs) were evaluated using cell viability, migration/invasion, tube formation, and spheroid-based 3D angiogenesis assays.
RESULTS
Hypoxic conditions caused significant increase in miR-1825 levels in OSCC cells and hiTDEs. miR-1825 alone and within hiTDEs promoted endothelial cell viability, migration, invasion, and angiogenic potential, which is reversed via inhibition of miR-1825 expression. miR-1825 within hiTDEs altered the angiogenesis potential of HUVEC cells via deregulation of TSC2/mTOR axis.
CONCLUSIONS
We showed that hypoxia led to OSCC-derived exosome mediated transfer of miR-1825 to HUVECs and enhanced angiogenesis in OSCC in vitro.
背景
口腔鳞状细胞癌（OSCC）的特点是血管生成增强，尽管诊断/治疗技术有所提高，但预后仍较差。在这里，我们旨在研究缺氧条件下 OSCC 来源的外泌体中包含的 miR-1825 对血管生成的潜在作用。
方法
使用细胞活力、迁移/侵袭、管形成和基于球体的 3D 血管生成测定，评估 miR-1825 模拟物/抑制剂以及缺氧诱导的肿瘤衍生外泌体对人脐静脉内皮细胞（HUVEC）的影响。
结果
缺氧条件导致 OSCC 细胞和 hiTDEs 中 miR-1825 水平显著增加。miR-1825 单独和在 hiTDEs 中促进内皮细胞活力、迁移、侵袭和血管生成潜力，通过抑制 miR-1825 表达可逆转这种作用。hiTDEs 中的 miR-1825 通过调节 TSC2/mTOR 轴改变了 HUVEC 细胞的血管生成潜力。
结论
我们表明，缺氧导致 OSCC 衍生的外泌体介导 miR-1825 转移到 HUVEC，并在体外增强了 OSCC 的血管生成。
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