人间充质干细胞来源的miR-3614-5p外泌体通过靶向IL7Rα抑制结直肠癌进展
Human mesenchymal stem cell-derived miR-3614-5p exosomes suppress progression of colorectal cancer by targeting IL7Rα.
摘要(中文译文)
结直肠癌（CRC）已成为日益加重的全球健康负担，尤其是在发展中国家。间充质干细胞（MSCs）已被报道可通过释放携带治疗性分子的外泌体部分抑制肿瘤进展。然而，工程化MSC来源的外泌体微小RNA（Exo-miRNA）在CRC中的治疗潜力仍很大程度上未被探索。通过血浆外泌体miRNA测序鉴定CRC中失调的miRNA。进行功能获得和功能缺失实验以评估候选miRNA在CRC细胞中的生物学效应。通过脂质体介导的转染对人间充质干细胞（hMSCs）进行工程化改造以过表达miR-3614-5p，并分离和鉴定富含miR-3614-5p的外泌体。在体外和体内评估工程化hMSC来源的外泌体miR-3614-5p（Exo-miR-3614-5p）对CRC进展的影响。进行机制研究以鉴定下游靶点和信号通路。miR-3614-5p被鉴定为在CRC中显著下调的治疗性miRNA。工程化hMSCs可高效地将miR-3614-5p装载至分泌的外泌体中。Exo-miR-3614-5p处理在体外显著抑制CRC细胞增殖，并在体内抑制肿瘤生长。在机制上，miR-3614-5p直接结合IL7Rα的3‘非翻译区（3’UTR），导致翻译抑制并随后使JAK2/STAT3信号通路失活。此外，miR-3614-5p对CRC表现出潜在的诊断价值。本研究表明，工程化hMSC来源的外泌体miR-3614-5p主要通过下调IL7Rα和抑制JAK2/STAT3信号通路有效抑制CRC进展。这些发现提示Exo-miR-3614-5p是CRC有前景的治疗和诊断候选物。
Abstract
Colorectal cancer (CRC) represents a growing global health burden, particularly in developing countries. Mesenchymal stem cells (MSCs) have been reported to suppress tumor progression partly through the release of exosomes that deliver therapeutic molecules. However, the therapeutic potential of engineered MSC-derived exosomal microRNAs (Exo-miRNAs) in CRC remains largely unexplored. Plasma exosome miRNA sequencing was performed to identify dysregulated miRNAs in CRC. Gain- and loss-of-function assays were conducted to evaluate the biological effects of candidate miRNAs in CRC cells. Human mesenchymal stem cells (hMSCs) were engineered to overexpress miR-3614-5p via Lipofectamine-mediated transfection, and exosomes enriched with miR-3614-5p were isolated and characterized. The effects of engineered hMSC-derived exosomal miR-3614-5p (Exo-miR-3614-5p) on CRC progression were assessed both in vitro and in vivo. Mechanistic studies were performed to identify downstream targets and signaling pathways. miR-3614-5p was identified as a therapeutic miRNA that was significantly downregulated in CRC. Engineered hMSCs efficiently loaded miR-3614-5p into secreted exosomes. Treatment with Exo-miR-3614-5p markedly suppressed CRC cell proliferation in vitro and inhibited tumor growth in vivo. Mechanistically, miR-3614-5p directly bound to the 3' untranslated region (3'UTR) of IL7Rα, resulting in translational repression and subsequent inactivation of the JAK2/STAT3 signaling pathway. In addition, miR-3614-5p exhibited potential diagnostic value for CRC. This study demonstrates that engineered hMSC-derived exosomal miR-3614-5p effectively inhibits CRC progression primarily through downregulation of IL7Rα and suppression of the JAK2/STAT3 signaling pathway. These findings suggest that Exo-miR-3614-5p represents a promising therapeutic and diagnostic candidate for CRC.
如何引用
AMA
Mengling Ye, Yingzhen Bian, Yanyan Lin, Shirong Li, Lixia Jiang, Jinlu Wu, et al. Human mesenchymal stem cell-derived miR-3614-5p exosomes suppress progression of colorectal cancer by targeting IL7Rα.. Journal of translational medicine. 2026; doi:10.1186/s12967-026-07859-y.
APA
Mengling Ye, Yingzhen Bian, Yanyan Lin, Shirong Li, Lixia Jiang, Jinlu Wu, et al (2026). Human mesenchymal stem cell-derived miR-3614-5p exosomes suppress progression of colorectal cancer by targeting IL7Rα.. Journal of translational medicine. https://doi.org/10.1186/s12967-026-07859-y
GB/T 7714
Mengling Ye, Yingzhen Bian, Yanyan Lin, Shirong Li, Lixia Jiang, Jinlu Wu, et al. Human mesenchymal stem cell-derived miR-3614-5p exosomes suppress progression of colorectal cancer by targeting IL7Rα.[J]. Journal of translational medicine, 2026 doi:10.1186/s12967-026-07859-y.
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