A new role for microRNAs, as ligands of Toll-like receptors

被引:117
作者
Fabbri, Muller [1 ]
Paone, Alessio [2 ]
Calore, Federica [2 ]
Galli, Roberta [2 ]
Croce, Carlo M. [2 ]
机构
[1] Univ So Calif, Keck Sch Med, Dept Pediat & Mol Microbiol & Immunol,Childrens H, Norris Comprehens Canc Ctr,Childrens Ctr Canc & B, Los Angeles, CA 90033 USA
[2] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
关键词
microRNAs; Toll-like receptors; tumor microenvironment; IL-6; TNF-alpha; metastasis; exosomes; IMMUNE-RESPONSE MODIFIERS; NF-KAPPA-B; CYTOKINE PRODUCTION; EXOSOME RELEASE; DENDRITIC CELLS; TUMOR-GROWTH; LUNG-CANCER; INFLAMMATION; MECHANISM; INDUCTION;
D O I
10.4161/rna.23144
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tumor microenvironment plays a central role in the development and dissemination of cancer cells. In addition to studying each specific cellular component of the microenvironment it has become clear that it is the type and amount of information that cells exchange that ultimately affects cancer phenotype. Recently, it has been discovered that intercellular communication occurs through the release of microvesicles and exosomes, whose cargo represents the information released by one cell to a recipient cell. A key component of this cargo is represented by microRNAs (miRNAs), small non-coding RNAs with gene regulatory functions. We discovered that miRNAs released by cancer cells within microvesicles can reach and bind to Toll-like receptors (TLRs) in surrounding immune cells, and activate them in a paracrine loop. As a result, immune cells produce cytokines that increase cell proliferation and metastatic potential. This discovery provides the rationale for the development of new drugs that might be used in the treatment of cancer as well as other inflammation-related diseases.
引用
收藏
页码:169 / 174
页数:6
相关论文
共 80 条
[1]   Pathogen recognition and innate immunity [J].
Akira, S ;
Uematsu, S ;
Takeuchi, O .
CELL, 2006, 124 (04) :783-801
[2]   The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance [J].
Allavena, Paola ;
Sica, Antonio ;
Garlanda, Cecilia ;
Mantovani, Alberto .
IMMUNOLOGICAL REVIEWS, 2008, 222 :155-161
[3]   MicroRNA functions in animal development and human disease [J].
Alvarez-Garcia, I ;
Miska, EA .
DEVELOPMENT, 2005, 132 (21) :4653-4662
[4]  
Ardies C Murray, 2003, Integr Cancer Ther, V2, P238, DOI 10.1177/1534735403256332
[5]   Tumour-derived microvesicles modulate biological activity of human monocytes [J].
Baj-Krzyworzeka, Monika ;
Szatanek, Rafal ;
Weglarczyk, Kazimierz ;
Baran, Jaroslaw ;
Zembala, Marek .
IMMUNOLOGY LETTERS, 2007, 113 (02) :76-82
[6]   Cancer - An inflammatory link [J].
Balkwill, F ;
Coussens, LM .
NATURE, 2004, 431 (7007) :405-406
[7]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[8]   TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex [J].
Blanchard, N ;
Lankar, D ;
Faure, F ;
Regnault, A ;
Dumont, C ;
Raposo, G ;
Hivroz, C .
JOURNAL OF IMMUNOLOGY, 2002, 168 (07) :3235-3241
[9]   MicroRNA control of lifespan and metabolism [J].
Boehm, Michelle ;
Slack, Frank J. .
CELL CYCLE, 2006, 5 (08) :837-840
[10]   Exosomes/microvesicles as a mechanism of cell-to-cell communication [J].
Camussi, Giovanni ;
Deregibus, Maria C. ;
Bruno, Stefania ;
Cantaluppi, Vincenzo ;
Biancone, Luigi .
KIDNEY INTERNATIONAL, 2010, 78 (09) :838-848