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. © 2012 The Authors.

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

Magri L.;Casazza A.;Mazzone M.;Naldini L.;De Palma M.
2012-01-01

Abstract

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. © 2012 The Authors.
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Animals; Base Pairing; Base Sequence; Bone Marrow Cells; Cell Line; Cell Line, Tumor; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematopoiesis; Humans; Immunophenotyping; Lectins, C-Type; Macrophages; Mannose Receptor; Mannose-Binding Lectins; Mice; Mice, Inbred C57BL; MicroRNAs; Molecular Sequence Data; Neoplasms; Nucleic Acid Conformation; RNA Precursors; Receptors, Cell Surface; rho-Associated Kinases
Squadrito M.L.; Pucci F.; Magri L.; Moi D.; Gilfillan G.D.; Ranghetti A.; Casazza A.; Mazzone M.; Lyle R.; Naldini L.; De Palma M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1841516
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