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Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis
Open accessAbstract
Cancer-secreted microRNAs (miRNAs) are emerging mediators of cancer-host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in nonmetastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. miR-105 can be detected in the circulation at the premetastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer.
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“Many studies have also demonstrated that extracellular miRNAs can exert biological functions in recipient cells to regulate their activity, thereby acting as intercellular signaling molecules.”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [134]
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“MiR-105 interferes with endothelial wall integrity by disrupting tight junctions through regulation of expression of the TJP-1 gene [134].”
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MicroRNAs, Regulatory Messengers Inside and Outside Cancer Cells
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Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4
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Metadata
- Authors
- Zhou, W., Fong, M. Y., Min, Y., Somlo, G., Liu, L., Palomares, M. R., Yu, Y., Chow, A., O’Connor, S. T. F., Chin, A. R., Yen, Y., Wang, Y., Marcusson, E. G., Chu, P., Wu, J., Wu, X., Li, A. X., Li, Z., Gao, H., Ren, X., Boldin, M. P., Lin, P. C., & Wang, S. E.
- Affiliations
- City Of Hope National Medical Center (US)
- National Cancer Institute (US)
- Regulus Therapeutics (United States) (US)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Corresponding author
- Wang, Shizhen Emily
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 25
- Issue
- 4
- Pages
- 501-515
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4016197
- OpenAlex
- W2143839116
- Cited by
- 1,476
- References
- 62
- Citations by year
- 2026: 61 · 2025: 91 · 2024: 113 · 2023: 145 · 2022: 164 · 2021: 175 · 2020: 148 · 2019: 152 · 2018: 118 · 2017: 111 · 2016: 97 · 2015: 72 · 2014: 28
- FWCI
- 32.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Association for Cancer Research
- Breast Cancer Research Foundation (12-60-26-WANG)
- Celgene
- National Institutes of Health
- National Key Research and Development Program of China (2012CB9333004)
- National Cancer Institute (P30CA-33572, R01CA166020, R01CA163586, P30CA033572)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- miR-105, metastasis, breast cancer, ZO-1, tight junctions, endothelial barrier integrity, exosomes, vascular permeability, metastatic progression
- MeSH terms
- Breast Neoplasms, Cell Movement, Endothelium, Vascular, Female, Humans, Neoplasm Metastasis, Biomarkers, Tumor, MicroRNAs, Cell Line, Tumor, Cell Growth Processes
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