Cited by 222Extracellular vesicles in diseaseMicroRNA in disease regulationCancer Cells and Metastasis

Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via mesothelial-to-mesenchymal transition

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Li, Qiang, Li, Bowen, Li, Qing, Wei, Song, He, Zhongyuan, Huang, Xiaoxu, Wang, Lu, Xia, Yiwen +6 more·2018·Cell Death & Disease

Abstract

Peritoneal metastasis is a primary metastatic route for gastric cancers, and the mechanisms underlying this process are still unclear. Peritoneal mesothelial cells (PMCs) undergo mesothelial-to-mesenchymal transition (MMT) to provide a favorable environment for metastatic cancer cells. In this study, we investigated how the exosomal miR-21-5p induces MMT and promotes peritoneal metastasis. Gastric cancer (GC)-derived exosomes were identified by transmission electron microscopy and western blot analysis, then the uptake of exosomes was confirmed by PKH-67 staining. The expression of miR-21-5p and SMAD7 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, and the interactions between miR-21-5p and its target genes SMAD7 were confirmed by Luciferase reporter assays. The MMT of PMCs was determined by invasion assays, adhesion assays, immunofluorescent assay, and western blot. Meanwhile, mouse model of tumor peritoneal dissemination model was performed to investigate the role of exosomal miR-21-5p in peritoneal metastasis in vivo. We found that PMCs could internalize GC-derived exosomal miR-21-5p and led to increased levels of miR-21-5p in PMCs. Through various types of in vitro and in vivo assays, we confirmed that exosomal miR-21-5p was able to induce MMT of PMCs and promote tumor peritoneal metastasis. Moreover, our study revealed that this process was promoted by exosomal miR-21-5p through activating TGF-β/Smad pathway via targeting SMAD7. Altogether, our data suggest that exosomal miR-21-5p induces MMT of PMCs and promote cancer peritoneal dissemination by targeting SMAD7. The exosomal miR-21-5p may be a novel therapeutic target for GC peritoneal metastasis.

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Authors
Li, Q., Li, B., Li, Q., Wei, S., He, Z., Huang, X., Wang, L., Xia, Y., Xu, Z., Li, Z., Wang, W., Yang, L., Zhang, D., & Xu, Z.
Affiliations
Jiangsu Province Hospital (CN)
Corresponding author
Zhang, Diancai
Venue
Cell Death & Disease
Published
2018-08-28
Volume
9
Issue
9
Pages
854-854
ISSN
2041-4889 (ISSN-L)
OpenAlex
W2889190369
Cited by
219
References
47
Citations by year
2026: 11 · 2025: 21 · 2024: 31 · 2023: 34 · 2022: 45 · 2021: 46 · 2020: 17 · 2019: 14
FWCI
7.03
Type
journal article
Language
en
Open access
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China (JX10231801, 30901443)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, JX10231801, JX 10231801)
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
gastric cancer, peritoneal carcinomatosis, exosomes, miR-21-5p, mesothelial-to-mesenchymal transition, peritoneal mesothelial cells, Smad7, TGF-β/Smad signaling, extracellular vesicles, tumor microenvironment
MeSH terms
Animals, Cell Movement, Epithelium, Female, Humans, Male, Mice, Nude, Middle Aged, Neoplasm Metastasis, Peritoneal Neoplasms, Peritoneum, Stomach Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Mice, Smad7 Protein, Exosomes, Epithelial-Mesenchymal Transition

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