PPARγ suppresses the proliferation of cardiac myxoma cells through downregulation of MEF2D in a miR-122-dependent manner.
Peroxisome proliferator-activated receptor gamma (PPARγ), 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 PPARγ is inversely correlated with that of myocyte enhancer factor 2D (MEF2D), a biomarker of CM. We found that activation of PPARγ 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 PPARγ suppress the proliferation of CM cells. These results suggest that PPARγ may exert its antiproliferative effects by negatively regulating the MEF2D in CM cells, which through upregulation of miR-122, and PPARγ/miR-122/MEF2D signaling pathway may be a novel target for treatment of CM.
Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Youzhu
Y
Qiu
Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Jie
J
Yang
Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Shizhu
S
Bian
Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Guozhu
G
Chen
Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, China. Electronic address: simpls@163.com.
Jie
J
Yu
D049109:Cell Proliferation; D015536:Down-Regulation; D006338:Heart Neoplasms / Q000378:metabolism*; D006801:Humans; D064326:MEF2 Transcription Factors / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D009232:Myxoma / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma
Cardiac myxoma; MEF2D; PPARγ; Proliferation; miR-122