MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation.
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.
Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom.
Anne
A
Aucher
Dominika
D
Rudnicka
Daniel M
DM
Davis
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002450:Cell Communication; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D055354:Exosomes; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism*; D034801:Mastocytoma / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D050777:Stathmin / Q000096:biosynthesis / Q000235:genetics; D053778:Thiazolidines / Q000494:pharmacology; D014162:Transfection
D019086:Bridged Bicyclo Compounds, Heterocyclic; D035683:MicroRNAs; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1; D011993:Recombinant Fusion Proteins; D050777:Stathmin; D053778:Thiazolidines; C555159:MIRN142 microRNA, human; C525067:MIR223, human; C493995:STMN1 protein, human; C037067:latrunculin A