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Updated: May 6, 2026
An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
Published on: May 21, 2019
MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation
Anne Aucher1, Dominika Rudnicka, Daniel M Davis
1Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom.
Abstract:
Recent research has indicated a new mode of intercellular communication facilitated by the movement of RNA between cells. There is evidence that RNA can transfer between cells in a multitude of ways, including in complex with proteins or lipids or in vesicles, including apoptotic bodies and exosomes. However, there remains little understanding of the function of nucleic acid transfer between human cells. In this article, we report that human macrophages transfer microRNAs (miRNAs) to hepato-carcinoma cells (HCCs) in a manner that required intercellular contact and involved gap junctions. Two specific miRNAs transferred efficiently between these cells--miR-142 and miR-223--and both were endogenously expressed in macrophages and not in HCCs. Transfer of these miRNAs influenced posttranscriptional regulation of proteins in HCCs, including decreased expression of reporter proteins and endogenously expressed stathmin-1 and insulin-like growth factor-1 receptor. Importantly, transfer of miRNAs from macrophages functionally inhibited proliferation of these cancerous cells. Thus, these data led us to propose that intercellular transfer of miRNA from immune cells could serve as a new defense against unwanted cell proliferation or tumor growth.
Insights
Human macrophages transfer microRNAs (miRNAs) to cancer cells, inhibiting their proliferation. This intercellular communication via gap junctions reveals a novel immune defense mechanism against tumor growth.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Intercellular communication via RNA transfer is a newly identified phenomenon.
- Mechanisms and functions of RNA transfer between human cells are not well understood.
Purpose of the Study:
- To investigate the transfer of microRNAs (miRNAs) from human macrophages to hepato-carcinoma cells (HCCs).
- To determine the functional impact of this miRNA transfer on cancer cell proliferation.
Main Methods:
- Investigated intercellular transfer of miRNAs between macrophages and HCCs requiring cell contact and gap junctions.
- Quantified transfer of specific miRNAs (miR-142, miR-223) using endogenous expression in macrophages.
- Assessed the impact of miRNA transfer on posttranscriptional gene regulation and proliferation in HCCs.
Main Results:
- Human macrophages transferred specific miRNAs (miR-142, miR-223) to HCCs via gap junctions.
- Transferred miRNAs regulated protein expression in HCCs, decreasing reporter proteins, stathmin-1, and IGF-1R.
- Macrophage-derived miRNA transfer functionally inhibited HCC proliferation.
Conclusions:
- Intercellular transfer of miRNAs from immune cells to cancer cells represents a novel mechanism of intercellular communication.
- This process, involving gap junctions, can inhibit cancer cell proliferation, suggesting a potential immune defense against tumors.
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