MiR-27b targets PPARγ to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells

The peroxisome proliferators-activated receptor (PPAR)gamma pathway is involved in cancer, but it appears to have both tumor suppressor and oncogenic functions. In neuroblastoma cells, miR-27b targets the 30 untranslated region of PPAR gamma and inhibits its mRNA and protein expression. miR-27b overexpression or PPAR gamma inhibition blocks cell growth in vitro and tumor growth in mouse xenografts. PPAR gamma activates expression of the pH regulator NHE1, which is associated with tumor progression. Lastly, miR-27b through PPAR gamma regulates nuclear factor-kappa B activity and transcription of inflammatory target genes. Thus, in neuroblastoma, miR-27b functions as a tumor suppressor by inhibiting the tumor-promoting function of PPAR gamma, which triggers an increased inflammatory response. In contrast, in breast cancer cells, PPAR gamma inhibits NHE1 expression and the inflammatory response, and it functions as a tumor suppressor. We suggest that the ability of PPAR gamma to promote or suppress tumor formation is linked to cell type-specific differences in regulation of NHE1 and other target genes. Oncogene (2012) 31, 3818-3825; doi: 10.1038/onc.2011.543; published online 28 November 2011