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Title: miR-511-3p modulates genetic programs of tumor-associated macrophages
Authors: Squadrito, Mario Leonardo ×
Pucci, Ferdinando
Magri, Laura
Moi, Davide
Gilfillan, Gregor D
Ranghetti, Anna
Casazza, Andrea
Mazzone, Max
Lyle, Robert
Naldini, Luigi
De Palma, Michele #
Issue Date: Feb-2012
Series Title: Cell reports vol:1 issue:2 pages:141-154
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.
URI: 
ISSN: 2211-1247
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Oncology and Angiogenesis (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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