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Cited by 551Extracellular vesicles in diseaseMicroRNA in disease regulationNanoparticle-Based Drug Delivery

Intercellular nanovesicle-mediated microRNA transfer: A mechanism of environmental modulation of hepatocellular cancer cell growth

Open access
Kogure, Takayuki, Lin, Wen-Lang, Yan, Irene K., Braconi, Chiara, Patel, Tushar·2011·Hepatology
DOI 10.1002/hep.24504PMC PMC3310362
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Abstract

Hepatocellular carcinoma (HCC) is characterized by a propensity for multifocality, growth by local spread, and dysregulation of multiple signaling pathways. These features may be determined by the tumoral microenvironment. The potential of tumor cells to modulate HCC growth and behavior by secreted proteins has been extensively studied. In contrast, the potential for genetic modulation is poorly understood. We investigated the role and involvement of tumor-derived nanovesicles capable of altering gene expression and characterized their ability to modulate cell signaling and biological effects in other cells. We show that HCC cells can produce nanovesicles and exosomes that differ in both RNA and protein content from their cells of origin. These can be taken up and internalized by other cells and can transmit a functional transgene. The microRNA (miRNA) content of these exosomes was examined, and a subset highly enriched within exosomes was identified. A combinatorial approach to identify potential targets identified transforming growth factor β activated kinase-1 (TAK1) as the most likely candidate pathway that could be modulated by these miRNAs. Loss of TAK1 has been implicated in hepatocarcinogenesis and is a biologically plausible target for intercellular modulation. We show that HCC cell-derived exosomes can modulate TAK1 expression and associated signaling and enhance transformed cell growth in recipient cells. Conclusion : Exosome-mediated miRNA transfer is an important mechanism of intercellular communication in HCC cells. These observations identify a unique intercellular mechanism that could potentially contribute to local spread, intrahepatic metastases, or multifocal growth in HCC. (Hepatology 2011;)

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  • Extracellular vesicles can transfer RNAs such as non-coding RNAs from one cell to another and thereby contribute to inter-cellular communication.

    “Recent studies have confirmed that EV can transfer RNAs such as ncRNAs from one cell to another and thereby contribute to important roles in inter-cellular communication (3–9).”

    From Analysis of Extracellular RNA by Digital PCR (2014) · cites this paper as [8]

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Research works printed but not linked: 25

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Cited by

Sorted by citations

Authors
Kogure, T., Lin, W.-L., Yan, I. K., Braconi, C., & Patel, T.
Affiliations
  • Mayo Clinic in Florida (US)
  • The Ohio State University (US)
Corresponding author
Patel, Tushar
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-10
Volume
54
Issue
4
Pages
1237-1248
ISSN
0270-9139 (ISSN-L)
DOI
10.1002/hep.24504
PMC
PMC3310362
OpenAlex
W1982255083
Cited by
551
References
2
Citations by year
2026: 15 · 2025: 16 · 2024: 16 · 2023: 18 · 2022: 34 · 2021: 41 · 2020: 52 · 2019: 40 · 2018: 50 · 2017: 46 · 2016: 45 · 2015: 48 · 2014: 56 · 2013: 35 · 2012: 30
FWCI
16.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK069370)
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
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
hepatocellular carcinoma, exosomes, microRNA transfer, intercellular communication, TAK1, tumor microenvironment, intrahepatic metastasis, multifocality, cell growth regulation
MeSH terms
Cell Communication, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Neoplasm Invasiveness, Sampling Studies, Tumor Cells, Cultured, Signal Transduction, MicroRNAs, Cell Proliferation, Exosomes, Tumor Microenvironment, Real-Time Polymerase Chain Reaction

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