miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1

Oncotarget. 2016 May 31;7(22):32421-32. doi: 10.18632/oncotarget.8718.

Abstract

We previously reported that miR-1207-5p can inhibit epithelial-mesenchymal transition (EMT) induced by growth factors such as EGF and TGF-β, but the exact mechanism is unclear. Here we identified that Colony stimulating factor 1 (CSF1) is a target gene of miR-1207-5p. CSF1 controls the production, differentiation and function of macrophage and promotes the release of proinflammatory chemokines. We showed that miR-1207-5p inhibited lung cancer cell A549 proliferation, migration and invasion in vitro, and suppressed the STAT3 and AKT signalings. miR-1207-5p overexpression can increase HUVEC angiogenesis, and can modulate the M2 phenotype of macrophage. miR-1207-5p also significantly inhibited A549 cells metastasis in a nude mouse xenograft model. miR-1207-5p and CSF1 expression levels and their relationship with lung cancer survival and metastasis status were assayed by means of a lung cancer tissue microarray. Macrophage is an essential part of the tumor microenvironment, thus the miR-1207-5p-CSF1 axis maybe a new regulator of lung cancer development through modulating the tumor microenvironment.

Keywords: CSF1; lung cancer; macrophage; miR-1207-5p; tumor microenvironment.

MeSH terms

  • A549 Cells
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • HEK293 Cells
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Macrophage Colony-Stimulating Factor / biosynthesis
  • Macrophage Colony-Stimulating Factor / genetics*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • Tissue Array Analysis
  • Transfection
  • Tumor Microenvironment
  • Xenograft Model Antitumor Assays

Substances

  • MIRN1207 microRNA, human
  • MicroRNAs
  • Macrophage Colony-Stimulating Factor