Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, 100053, Beijing, PR China.
Mol Biol Rep. 2022 Oct;49(10):9275-9281. doi: 10.1007/s11033-022-07763-w. Epub 2022 Aug 21.
Tumor hypoxia is a feature of tumor micro-environment (TME), which provides a suitable environment for tumor cells migration and invasion. However, up to now, the function of exosomes derived from hypoxic tumor cells is still not fully understood. The present study is aimed to explore the underlying mechanisms of lung cancer-secreted exosomes-mediated tumor metastasis under hypoxia.
METHODS & RESULTS: Exosomes were isolated from normoxic or hypoxic NCI-H446 cells. Some characteristic proteins were detected by western blots. Levels of CD63, CD 9 and CD 81 proteins were up-regulated on the membrane of exosomes secreted by hypoxic NCI-H446 cells. Basing on the results from miRNA sequencing, qRT-PCR and wound healing assay, hsa-miR-625-3p was discovered to be accumulated inside hypoxic exosomes and responsible for the metastasis of lung cancer cell. Further experiments from luciferase reporter gene assay demonstrated hsa-miR-625-3p could directly inhibit SCAI expression through binding with its 3'UTR, which suggested the mechanisms by which exosomal hsa-miR-625-3p suppressed tumor cells migration.
Exosomal miR-625-3p derived from hypoxic small lung cancer cells accelerated tumor cells migration through inhibiting SCAI directly.
肿瘤缺氧是肿瘤微环境（TME）的一个特征，它为肿瘤细胞的迁移和侵袭提供了适宜的环境。然而，迄今为止，缺氧肿瘤细胞来源的外泌体的功能仍未完全了解。本研究旨在探讨低氧条件下肺癌细胞分泌的外泌体介导肿瘤转移的潜在机制。
从 NCI-H446 细胞的常氧或低氧条件下分离出外泌体。通过 Western blot 检测到一些特征性蛋白。低氧 NCI-H446 细胞分泌的外泌体膜上 CD63、CD9 和 CD81 蛋白水平上调。基于 miRNA 测序、qRT-PCR 和划痕愈合实验的结果，发现 hsa-miR-625-3p 在低氧外泌体中积累，并负责肺癌细胞的转移。进一步的荧光素酶报告基因实验表明，hsa-miR-625-3p 通过与 SCAI 的 3'UTR 结合直接抑制 SCAI 的表达，这表明外泌体 hsa-miR-625-3p 通过直接抑制肿瘤细胞迁移的机制。
低氧小肺癌细胞来源的外泌体 miR-625-3p 通过直接抑制 SCAI 加速肿瘤细胞迁移。
