Journal
CELL DEATH DISCOVERY
Volume 7, Issue 1, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41420-021-00611-z
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Funding
- National Natural Science Foundation of China [81972214, 81302065, 81772932, 81201535, 81472202]
- Scientific Research Fund Project of Anhui Medical University [2018xkj058]
- Shanghai Natural Science Foundation [20ZR1472400]
- Key Program of Hunan Provincial Department of Science and Technology [2020WK2020]
- Construction of Clinical Medical Center for Tumor Biological Samples in Nantong [HS2016004]
- Nantong Science and Technology Project [JC2018125]
- Wu Jieping Medical Foundation [320.6750.14326]
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Exosomal miR-15a derived from MSCs can inhibit the proliferative, migrating, and invasive abilities of HCC cells by downregulating SALL4 expression. The exosomes successfully deliver miR-15a to HCC cells, leading to decreased tumorigenicity and metastasis of HCC tumors. In vivo experiments in nude mice further confirmed the inhibitory effects of exosomal miR-15a on HCC development.
Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.
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