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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)141-154
Number of pages14
JournalCell Reports
Volume1
Issue number2
DOIs
Publication statusPublished - Feb 23 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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. (2012). MiR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages. Cell Reports, 1(2), 141-154. https://doi.org/10.1016/j.celrep.2011.12.005