miR-511-3p modulates genetic programs of tumor-associated macrophages

Cell Rep. 2012 Feb 23;1(2):141-54. doi: 10.1016/j.celrep.2011.12.005. Epub 2012 Feb 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Pairing / genetics
  • Base Sequence
  • Bone Marrow Cells / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Hematopoiesis / genetics
  • Humans
  • Immunophenotyping
  • Lectins, C-Type / genetics
  • Macrophages / metabolism*
  • Mannose-Binding Lectins / genetics
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / chemistry
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Neoplasms / blood supply
  • Neoplasms / genetics*
  • Neoplasms / pathology*
  • Nucleic Acid Conformation
  • RNA Precursors / chemistry
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • Receptors, Cell Surface / genetics
  • rho-Associated Kinases / metabolism

Substances

  • Lectins, C-Type
  • MIRN511 microRNA, human
  • Mannose-Binding Lectins
  • MicroRNAs
  • Mirn511 microRNA, mouse
  • RNA Precursors
  • Receptors, Cell Surface
  • mannose receptor
  • ROCK2 protein, human
  • Rock2 protein, mouse
  • rho-Associated Kinases

Associated data

  • GEO/GSE34903