1. Oxaliplatin-induced upregulation of exosomal miR-424-3p derived from human bone marrow mesenchymal stem cells attenuates progression of gastric cancer cells.
- Author
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Shen W, Wei C, Li N, Yu W, Yang X, and Luo S
- Subjects
- Humans, Animals, Mice, Cell Line, Tumor, Up-Regulation, Gene Expression Regulation, Neoplastic drug effects, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Tumor Microenvironment, Mice, Nude, Disease Progression, MicroRNAs genetics, MicroRNAs metabolism, Oxaliplatin pharmacology, Mesenchymal Stem Cells metabolism, Exosomes metabolism, Exosomes genetics, Stomach Neoplasms pathology, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, Stomach Neoplasms drug therapy, Epithelial-Mesenchymal Transition drug effects, Epithelial-Mesenchymal Transition genetics
- Abstract
Chemotherapy, particularly with oxaliplatin, is a key treatment for advanced gastric cancer (GC), and exosomes derived from human bone marrow mesenchymal stem cells (hBM-MSCs) play a vital role in the tumor microenvironment. The study aims to elucidate the previously unexplored role of exosomes derived from hBM-MSCs in GC tumorigenesis, especially under the influence of chemotherapy. We conducted an experimental study, utilizing miRNA sequencing and biological experiments, to analyze the tumorigenicity of exosomal miR-424-3p secreted by hBM-MSCs and its target gene RHOXF2 in GC cell lines. The results were confirmed through experimentation using a xenograft mouse model. This study demonstrated the role of hBM-MSCs in the GC microenvironment, focusing on their epithelial-mesenchymal transition (EMT) facilitation through exosomes, which led to enhanced tumorigenicity in GC cells. Intriguingly, this pro-tumor effect was abrogated when hBM-MSCs were treated with oxaliplatin. Exosomal miRNA sequencing revealed that oxaliplatin can upregulate the levels of miR-424-3p in exosomes secreted by hBM-MSCs, thereby inhibiting the EMT process in GC cells. Furthermore, miR-424-3p was identified to target and downregulate RHOXF2 expression, impeding the malignant behavior of GC cells both in vitro and in the mouse model. These findings uncover a potential hidden mechanism of oxaliplatin's anti-tumor action and propose the delivery of miR-424-3p via exosomes as a promising avenue for anti-tumor therapy., (© 2024. The Author(s).)
- Published
- 2024
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