miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2012-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124711000155 |
| _version_ | 1818211455449694208 |
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| author | Mario Leonardo Squadrito Ferdinando Pucci Laura Magri Davide Moi Gregor D. Gilfillan Anna Ranghetti Andrea Casazza Massimiliano Mazzone Robert Lyle Luigi Naldini Michele De Palma |
| author_facet | Mario Leonardo Squadrito Ferdinando Pucci Laura Magri Davide Moi Gregor D. Gilfillan Anna Ranghetti Andrea Casazza Massimiliano Mazzone Robert Lyle Luigi Naldini Michele De Palma |
| author_sort | Mario Leonardo Squadrito |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T05:32:46Z |
| format | Article |
| id | doaj.art-7b15bca799014178ae7195ee22b1ec25 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T05:32:46Z |
| publishDate | 2012-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7b15bca799014178ae7195ee22b1ec252022-12-22T00:36:16ZengElsevierCell Reports2211-12472012-02-011214115410.1016/j.celrep.2011.12.005miR-511-3p Modulates Genetic Programs of Tumor-Associated MacrophagesMario Leonardo Squadrito0Ferdinando Pucci1Laura Magri2Davide Moi3Gregor D. Gilfillan4Anna Ranghetti5Andrea Casazza6Massimiliano Mazzone7Robert Lyle8Luigi Naldini9Michele De Palma10Angiogenesis and Tumor Targeting Unit, and HSR-TIGET, Division of Regenerative Medicine, San Raffaele Institute, 20132-Milan, ItalyAngiogenesis and Tumor Targeting Unit, and HSR-TIGET, Division of Regenerative Medicine, San Raffaele Institute, 20132-Milan, ItalyNeural Stem Cell Biology Unit, Division of Regenerative Medicine, San Raffaele Institute, 20132-Milan, ItalyAngiogenesis and Tumor Targeting Unit, and HSR-TIGET, Division of Regenerative Medicine, San Raffaele Institute, 20132-Milan, ItalyDepartment of Medical Genetics and Norwegian High-Throughput Sequencing Centre (NSC), Oslo University Hospital, Kirkeveien 166, 0407-Oslo, NorwayAngiogenesis and Tumor Targeting Unit, and HSR-TIGET, Division of Regenerative Medicine, San Raffaele Institute, 20132-Milan, ItalyLaboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB and K.U. Leuven, 3000 Leuven, BelgiumLaboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB and K.U. Leuven, 3000 Leuven, BelgiumDepartment of Medical Genetics and Norwegian High-Throughput Sequencing Centre (NSC), Oslo University Hospital, Kirkeveien 166, 0407-Oslo, NorwayAngiogenesis and Tumor Targeting Unit, and HSR-TIGET, Division of Regenerative Medicine, San Raffaele Institute, 20132-Milan, ItalyAngiogenesis and Tumor Targeting Unit, and HSR-TIGET, Division of Regenerative Medicine, San Raffaele Institute, 20132-Milan, ItalyExpression 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.http://www.sciencedirect.com/science/article/pii/S2211124711000155 |
| spellingShingle | Mario Leonardo Squadrito Ferdinando Pucci Laura Magri Davide Moi Gregor D. Gilfillan Anna Ranghetti Andrea Casazza Massimiliano Mazzone Robert Lyle Luigi Naldini Michele De Palma miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages Cell Reports |
| title | miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages |
| title_full | miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages |
| title_fullStr | miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages |
| title_full_unstemmed | miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages |
| title_short | miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages |
| title_sort | mir 511 3p modulates genetic programs of tumor associated macrophages |
| url | http://www.sciencedirect.com/science/article/pii/S2211124711000155 |
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