title: miR-511-3p modulates genetic programs of tumor-associated macrophages.
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.
authors: Angiogenesis and Tumor Targeting Unit, and HSR-TIGET, Division of Regenerative Medicine, San Raffaele Institute, 20132-Milan, Italy.
authors: Mario Leonardo
authors: ML
authors: Squadrito
authors: Ferdinando
authors: F
authors: Pucci
authors: Laura
authors: L
authors: Magri
authors: Davide
authors: D
authors: Moi
authors: Gregor D
authors: GD
authors: Gilfillan
authors: Anna
authors: A
authors: Ranghetti
authors: Andrea
authors: A
authors: Casazza
authors: Massimiliano
authors: M
authors: Mazzone
authors: Robert
authors: R
authors: Lyle
authors: Luigi
authors: L
authors: Naldini
authors: Michele
authors: M
authors: De Palma
mesh_terms: D000818:Animals; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000235:genetics; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D009690:Nucleic Acid Conformation; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; C578471:MIRN511 microRNA, human; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D035683:MicroRNAs; C578472:Mirn511 microRNA, mouse; D012322:RNA Precursors; D011956:Receptors, Cell Surface; C515852:ROCK2 protein, human; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases