Figure 11. SMAD4, regulated by microRNA-146a, promotes microglial cell migration and tumor progression in glioma environment.

Glioma cells secrete a number of factors including TGFβ (A) that activates the TGFβ pathway in microglia associated with glioma. Glioma conditioned medium was found to induce phosphorylation of SMAD2/3 complex and increase the level of SMAD4 (B) in microglia. Concurrently, miR-146a which was found to target SMAD4, was downregulated in glioma associated microglia (C). Downregulation of miR-146a in glioma-associated microglia increases the levels of tumor supportive factors (D), including SMAD4 and MMP9 which promote glioma progression and microglial migration.