Department of Medical Laboratory Center, General Hospital of Central Theatre Command of People's Liberation Arm, Wuhan, Hubei, China.
Oncology Department, Maoming Hospital of Traditional Chinese Medicine, Maoming, Guangdong, China.
J Biochem Mol Toxicol. 2024 Feb;38(2):e23656. doi: 10.1002/jbt.23656.
Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as circular RNAs (circRNAs) and microRNAs (miRNAs), between different cells. Human umbilical cord-derived mesenchymal stem cells (Hu-MSCs) can migrate to tumor sites and exert complex functions throughout tumor progression. In this study, we successfully isolated Hu-MSCs from human umbilical cords based on their surface marker expression. Hu-MSC-derived exosomes significantly reduced the invasion, migration, and proliferation of cholangiocarcinoma (CCA) cells. Furthermore, circ_0037104 was downregulated in CCA and inhibited the proliferation and metastasis of CCA cells. Then, we investigated the effect of Hu-MSC-derived exosomal circ_0037104 on CCA. Circ_0037104 mainly regulates miR-620 and enhances APAF1 expression, inhibiting CCA cell proliferation and metastasis. Overall, Hu-MSC exosomal circ_0037104 contributes to the progression and stemness of CCA cells via miR-620/APAF1. In conclusion, Hu-MSC-derived exosomal circ_0037104 sponges miR-620 directly and negatively targets APAF1 to suppress CCA.
外泌体是一种膜封闭的纳米囊泡,可在不同细胞之间传递环状 RNA(circRNA)和 microRNA(miRNA)等活性 cargo。人脐带间充质干细胞(Hu-MSCs)可以迁移到肿瘤部位,并在肿瘤进展过程中发挥复杂的功能。在这项研究中,我们基于表面标志物表达,成功地从人脐带中分离出 Hu-MSCs。Hu-MSC 来源的外泌体显著降低了胆管癌细胞的侵袭、迁移和增殖。此外,circ_0037104 在 CCA 中下调,并抑制了 CCA 细胞的增殖和转移。然后,我们研究了 Hu-MSC 来源的外泌体 circ_0037104 对 CCA 的影响。circ_0037104 主要调控 miR-620,增强 APAF1 的表达,抑制 CCA 细胞的增殖和转移。总的来说,Hu-MSC 外泌体 circ_0037104 通过 miR-620/APAF1 促进 CCA 细胞的进展和干性。总之,Hu-MSC 衍生的外泌体 circ_0037104 通过直接吸附 miR-620 并靶向 APAF1 负调控来抑制 CCA。