Peroxisome proliferator-activated receptor gamma (PPAR gamma), a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of cells proliferation. However, its effects on cardiac myxoma (CM) cells and the underlying signaling mechanism is unclear. In the present study, we demonstrated that the level of PPAR gamma is inversely correlated with that of myocyte enhancer factor 2D (MEF2D), a biomarker of CM. We found that activation of PPAR gamma inhibit MEF2D expression via upregulation of miR-122, which can target the 3'-UTR of MEF2D and inhibit MEF2D expression, by directly binding to the PPRE in the miR-122 promoter region. Functional experiments further showed that miR-122-dependent downregulation of MEF2D by PPAR gamma suppress the proliferation of CM cells. These results suggest that PPAR gamma may exert its antiproliferative effects by negatively regulating the MEF2D in CM cells, which through upregulation of miR-122, and PPAR gamma/miR-122/MEF2D signaling pathway may be a novel target for treatment of CM. (C) 2016 Elsevier Inc. All rights reserved.