title: MiR-27b targets PPARγ to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells.
abstract: The peroxisome proliferators-activated receptor (PPAR)γ pathway is involved in cancer, but it appears to have both tumor suppressor and oncogenic functions. In neuroblastoma cells, miR-27b targets the 3' untranslated region of PPARγ and inhibits its mRNA and protein expression. miR-27b overexpression or PPARγ inhibition blocks cell growth in vitro and tumor growth in mouse xenografts. PPARγ activates expression of the pH regulator NHE1, which is associated with tumor progression. Lastly, miR-27b through PPARγ regulates nuclear factor-κB activity and transcription of inflammatory target genes. Thus, in neuroblastoma, miR-27b functions as a tumor suppressor by inhibiting the tumor-promoting function of PPARγ, which triggers an increased inflammatory response. In contrast, in breast cancer cells, PPARγ inhibits NHE1 expression and the inflammatory response, and it functions as a tumor suppressor. We suggest that the ability of PPARγ to promote or suppress tumor formation is linked to cell type-specific differences in regulation of NHE1 and other target genes.
authors: Department Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors: J-J
authors: JJ
authors: Lee
authors: A
authors: A
authors: Drakaki
authors: D
authors: D
authors: Iliopoulos
authors: K
authors: K
authors: Struhl
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology; D000818:Animals; D027682:Cation Transport Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D051379:Mice; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D009447:Neuroblastoma / Q000473:pathology* / Q000517:prevention & control; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; D027682:Cation Transport Proteins; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers