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外泌体 circ_0037104 来源于 Hu-MSCs 通过海绵吸附 miR-620 和靶向 AFAP1 抑制胆管癌进展。

Exosomal circ_0037104 derived from Hu-MSCs inhibits cholangiocarcinoma progression by sponging miR-620 and targeting AFAP1.

机构信息

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.

出版信息

J Biochem Mol Toxicol. 2024 Feb;38(2):e23656. doi: 10.1002/jbt.23656.

Abstract

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.

摘要

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。

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