由间充质干细胞分泌的外泌体中的miR-99b-5p可以通过靶向FGFR3来延缓结直肠癌的进展。
Exosomal miR-99b-5p Secreted from Mesenchymal Stem Cells Can Retard the Progression of Colorectal Cancer by Targeting FGFR3.
发表日期:2023 Aug 31
作者:
Shufang Ning, Yusha Chen, Shirong Li, Mengshu Liu, Haizhou Liu, Mengling Ye, Chen Wang, Jinmiao Pan, Wene Wei, Jilin Li, Litu Zhang
来源:
Stem Cell Reviews and Reports
摘要:
人骨髓间充质干细胞(BMSCs)是高效的外泌体生产者,可以潜在地用于输送miRNA进行癌症治疗。本研究旨在评估MSC外泌体miR-99b-5p在结直肠癌(CRC)发展过程中的作用。同时,评估了使用血浆中miR-99b-5p外泌体水平来预测结直肠癌肝转移的潜在价值。在这项研究中,我们发现纤维母细胞生长因子受体3(FGFR3)的过表达与CRC肿瘤进展相关,FGFR3是miR-99b-5p的靶基因,在CRC组织中其表达水平下调。此外,我们观察到升高的miR-99b-5p抑制了CRC细胞的增殖、侵袭和迁移,而降低的miR-99b-5p水平则对CRC细胞产生了相反的效应。此外,由BMSCs输送的外泌体miR-99b-5p能够限制体外CRC细胞的增殖、侵袭和迁移,同时抑制体内肿瘤生长。综上所述,这些发现揭示了MSC来源的外泌体miR-99b-5p能够转移入CRC细胞,并通过靶向FGFR3来抑制肿瘤进展。这突显了外泌体miR-99b-5p作为CRC的新型诊断标志物的潜力,同时提供了一个用于对抗CRC的治疗靶标。© 2023. 作者或作者,以独家许可证授予施普林格科技(集团)有限公司,斯普林格自然出版集团的一部分。
Human bone marrow mesenchymal stem cells (BMSCs) are efficient mass producers of exosomes that can potentially be utilized for delivery of miRNAs in cancer therapy. The current study aimed to assess the role of MSC-exosomal miR-99b-5p during the development of colorectal cancer (CRC). The potential value of using plasma levels of exosomal miR-99b-5p for predicting the liver metastasis of colorectal cancer was also assessed. In this study, we found that overexpression of fibroblast growth factor receptor 3 (FGFR3) was associated with tumor progression in CRC and FGFR3 was the target gene of miR-99b-5p, which was down-regulated in CRC tissues. Furthermore, we observed that elevated miR-99b-5p inhibited CRC cell proliferation, invasion and migration, while reduced levels had the opposite effect on CRC cells. Moreover, exosomal miR-99b-5p delivered by BMSCs was able to limit the proliferation, invasion and migration of CRC cells in vitro, as well as suppressing tumor growth in vivo. Collectively, these findings revealed that MSC-derived exosomal miR-99b-5p can be transferred into CRC cells and which can suppress tumor progression by targeting FGFR3. This highlights the potential of using exosomal miR-99b-5p as a novel diagnostic marker for CRC, while providing a therapeutic target to combat CRC.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.