Histone demethylase KDM3C regulates the lncRNA GAS5–miR-495-3p–PHF8 axis in cardiac hypertrophy,Annals of the New York Academy of Sciences

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Histone demethylase KDM3C regulates the lncRNA GAS5–miR-495-3p–PHF8 axis in cardiac hypertrophy
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2022-07-01 , DOI: 10.1111/nyas.14813
Linlin Zhao ₁ , Feng Qi ₂ , Dongdong Du ₁ , Naishi Wu ₁

Affiliation

Cardiac hypertrophy (CH) is a pathological phenotype of cardiomyopathy. Epigenetic modification is a mechanism associated with CH. Our study here investigated the histone demethylase KDM3C in relation to epigenetic regulation in CH. We found that KDM3C mRNA silencing alleviated CH, as evidenced by reduced ANP, BNP, and β-MHC mRNAs, increased α-MHC mRNA, decreased cell surface area, and reduced cellular protein/DNA ratios. Specifically, KDM3C upregulated miR-200c-3p expression through demethylation of H3K9me2, leading to enhanced binding of miR-200c-3p to GAS5 and suppression of GAS5 expression; these effects then led to reduced binding of GAS5 to miR-495-3p, increased miR-495-3p expression, and repression of PHF8 transcription. Through these mechanisms, our data indicate that KDM3C-dependent epigenetic modification promotes CH.

中文翻译：

组蛋白去甲基化酶 KDM3C 调节心肌肥厚中的 lncRNA GAS5–miR-495-3p–PHF8 轴

心脏肥大（CH）是心肌病的一种病理表型。表观遗传修饰是与 CH 相关的机制。我们在这里的研究调查了组蛋白去甲基化酶 KDM3C 与 CH 表观遗传调控的关系。我们发现 KDM3C mRNA 沉默减轻了 CH，如减少的 ANP、BNP 和 β-MHC mRNA、增加的 α-MHC mRNA、减少的细胞表面积和降低的细胞蛋白质/DNA 比率所证明的。具体而言，KDM3C 通过 H3K9me2 的去甲基化上调 miR-200c-3p 的表达，从而增强 miR-200c-3p 与 GAS5 的结合并抑制 GAS5 的表达；然后，这些作用导致 GAS5 与 miR-495-3p 的结合减少、miR-495-3p 表达增加以及 PHF8 转录抑制。通过这些机制，我们的数据表明 KDM3C 依赖性表观遗传修饰促进了 CH。

更新日期：2022-07-01

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