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过氧化物酶体增殖物激活受体γ(PPARγ)通过以miR - 122依赖的方式下调心肌增强因子2D(MEF2D)来抑制心脏黏液瘤细胞的增殖。

PPARγ suppresses the proliferation of cardiac myxoma cells through downregulation of MEF2D in a miR-122-dependent manner.

作者信息

Qiu Youzhu, Yang Jie, Bian Shizhu, Chen Guozhu, Yu Jie

机构信息

Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

出版信息

Biochem Biophys Res Commun. 2016 Jun 3;474(3):560-565. doi: 10.1016/j.bbrc.2016.04.112. Epub 2016 Apr 22.

Abstract

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.

摘要

过氧化物酶体增殖物激活受体γ(PPARγ)是一种多功能转录因子,据报道其可通过抑制细胞增殖发挥抗肿瘤作用。然而,其对心脏黏液瘤(CM)细胞的作用及潜在信号机制尚不清楚。在本研究中,我们发现PPARγ的水平与CM的生物标志物——肌细胞增强因子2D(MEF2D)的水平呈负相关。我们发现,PPARγ的激活通过上调miR-122抑制MEF2D的表达,miR-122可通过直接结合miR-122启动子区域的PPRE靶向MEF2D的3'-UTR并抑制MEF2D的表达。功能实验进一步表明,PPARγ通过miR-122依赖的方式下调MEF2D可抑制CM细胞的增殖。这些结果表明,PPARγ可能通过负向调节CM细胞中的MEF2D发挥其抗增殖作用,这一过程通过上调miR-122实现,且PPARγ/miR-122/MEF2D信号通路可能是治疗CM的新靶点。

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