MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response

被引：1414

作者：

Fabbri, Muller ^{[1
]}

Paone, Alessio ^{[1
]}

Calore, Federica ^{[1
]}

Galli, Roberta ^{[1
]}

Gaudio, Eugenio ^{[1
]}

Santhanam, Ramasamy ^{[1
]}

Lovat, Francesca ^{[1
]}

Fadda, Paolo ^{[1
]}

Mao, Charlene ^{[1
]}

Nuovo, Gerard J. ^{[4
]}

Zanesi, Nicola ^{[1
]}

Crawford, Melissa ^{[2
]}

Ozer, Gulcin H. ^{[1
]}

Wernicke, Dorothee ^{[1
]}

Alder, Hansjuerg ^{[1
]}

Caligiuri, Michael A. ^{[3
]}

Nana-Sinkam, Patrick ^{[2
]}

Perrotti, Danilo ^{[1
]}

Croce, Carlo M. ^{[1
]}

机构：

[1] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA

[2] Ohio State Univ, Div Pulm Allergy Crit Care & Sleep Med, Ctr Comprehens Canc, Columbus, OH 43210 USA

[3] Ohio State Univ, Div Hematol, Ctr Comprehens Canc, Columbus, OH 43210 USA

[4] Phylogeny Inc, Columbus, OH 43210 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 31期

基金：

美国国家卫生研究院;

关键词：

microvesicles; cytokines; IL-6; TNF-alpha; STRANDED-RNA; RECOGNITION; CANCER; CELLS; ACTIVATION; MECHANISMS; CARCINOMA;

D O I：

10.1073/pnas.1209414109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

MicroRNAs (miRNAs) are small noncoding RNAs, 19-24 nucleotides in length, that regulate gene expression and are expressed aberrantly in most types of cancer. MiRNAs also have been detected in the blood of cancer patients and can serve as circulating biomarkers. It has been shown that secreted miRNAs within exosomes can be transferred from cell to cell and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs. Here we show that tumor-secreted miR-21 and miR-29a also can function by another mechanism, by binding as ligands to receptors of the Toll-like receptor (TLR) family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response that ultimately may lead to tumor growth and metastasis. Thus, by acting as paracrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is implicated in tumor-immune system communication and is important in tumor growth and spread, thus representing a possible target for cancer treatment.

引用

页码：E2110 / E2116

页数：7

共 21 条

[1]

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