miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages

被引：179

作者：

Squadrito, Mario Leonardo ^{[1
,3
,8
]}

Pucci, Ferdinando ^{[1
,3
,8
]}

Magri, Laura ^{[2
,3
]}

Moi, Davide ^{[1
,8
]}

Gilfillan, Gregor D. ^{[4
,5
]}

Ranghetti, Anna ^{[1
,8
]}

Casazza, Andrea ^{[6
,7
]}

Mazzone, Massimiliano ^{[6
,7
]}

Lyle, Robert ^{[4
,5
]}

Naldini, Luigi ^{[1
,3
,8
]}

De Palma, Michele ^{[1
,8
]}

机构：

[1] Ist Sci San Raffaele, HSR TIGET, Div Regenerat Med, I-20132 Milan, Italy

[2] Ist Sci San Raffaele, Div Regenerat Med, Neural Stem Cell Biol Unit, I-20132 Milan, Italy

[3] Univ Vita Salute San Raffaele, I-20132 Milan, Italy

[4] Oslo Univ Hosp, Dept Med Genet, N-0407 Oslo, Norway

[5] Oslo Univ Hosp, Norwegian High Throughput Sequencing Ctr NSC, N-0407 Oslo, Norway

[6] VIB, Vesalius Res Ctr, Lab Mol Oncol & Angiogenesis, B-3000 Louvain, Belgium

[7] Katholieke Univ Leuven, B-3000 Louvain, Belgium

[8] Ist Sci San Raffaele, Angiogenesis & Tumor Targeting Unit, I-20132 Milan, Italy

来源：

CELL REPORTS | 2012年 / 1卷 / 02期

基金：

欧洲研究理事会;

关键词：

ALTERNATIVE ACTIVATION; CANCER-THERAPY; MYELOID CELLS; MICRORNAS; MONOCYTES; DIFFERENTIATION; ANGIOGENESIS; RECOGNITION; METASTASIS; EXPRESSION;

D O I：

10.1016/j.celrep.2011.12.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Expression of the mannose receptor (MRC1/CD206) identifies macrophage subtypes, such as alternatively activated macrophages (AAMs) and M2-polarized tumor-associated macrophages (TAMs), which are endowed with tissue-remodeling, proangiogenic, and protumoral activity. However, the significance of MRC1 expression for TAM's protumoral activity is unclear. Here, we describe and characterize miR-511-3p, an intronic microRNA (miRNA) encoded by both mouse and human MRC1 genes. By using sensitive miRNA reporter vectors, we demonstrate robust expression and bioactivity of miR-511-3p in MRC1(+) AAMs and TAMs. Unexpectedly, enforced expression of miR-511-3p tuned down the protumoral gene signature of MRC1(+) TAMs and inhibited tumor growth. Our findings suggest that transcriptional activation of Mrc1 in TAMs evokes a genetic program orchestrated by miR-511-3p, which limits rather than enhances their protumoral functions. Besides uncovering a role for MRC1 as gatekeeper of TAM's protumoral genetic programs, these observations suggest that endogenous miRNAs may operate to establish thresholds for inflammatory cell activation in tumors.

引用

页码：141 / 154

页数：14

共 36 条

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