Aberrant G protein-receptor expression is associated with DNA methylation in aldosterone-producing adenoma
Aberrant G protein-receptor expression is associated with DNA methylation in aldosterone-producing adenoma
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DOI：
10.1016/j.mce.2017.08.019
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发表时间：
2018-02-05
影响因子：
4.1
通讯作者：
Hattori, Noboru
中科院分区：
文献类型：
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作者：
Itcho, Kiyotaka;Oki, Kenji;Hattori, Noboru
本研究旨在探讨G蛋白偶联受体（GPCR）相关基因的甲基化水平及甲基化对醛固酮生成腺瘤（APA） mRNA表达水平的影响。DNA甲基化阵列和转录组分析应用于无功能肾上腺皮质腺瘤（NFA）和APA。我们研究了192个gpcr相关基因，发现APA中66个基因的启动子区域存在低甲基化。微阵列与甲基化分析的整合研究显示，HTR4、MC2R、TACR1、GRM3和PTGER1在APA中表现出mRNA的低甲基化和上调。qPCR分析显示，APAs中HTR4和PTGER1的表达分别比NFA5高9.3倍和6.6倍，而其他基因的表达在组间无差异。转录起始位点229和666位置的HTR4和PTGER1甲基化与其mRNA水平呈显著负相关。在人肾上腺样本中，甲基化水平与KCNJ5或ATP1A1突变无关。我们证明了APA中gpcr相关基因的CpG岛去甲基化发生率增加。HTR4和PTGER1两种受体的表达与DNA甲基化密切相关。(C) 2017 Elsevier B.V.版权所有
This study aimed to evaluate the methylation levels of G protein-coupled receptor (GPCR) related genes and the effects of methylation on mRNA expression levels in aldosterone-producing adenoma (APA). DNA methylation array and transcriptome analysis were applied in non-functioning adrenocortical adenoma (NFA) and APA. We investigated 192 GPCR-related genes and found hypo-methylation in the promoter region of 66 of these genes in APA. An integration study between microarray and methylation analysis revealed that HTR4, MC2R, TACR1, GRM3, and PTGER1 showed hypo-methylation and up-regulation of mRNA in APA. qPCR analysis showed that HTR4 and PTGER1 expression was 9.3-fold and 6.6-fold higher in APAs than in NFA5, respectively, whereas expression of the other genes was not different between the groups. Methylation of HTR4 and PTGER1 at positions 229 and 666 from the transcription start site, respectively, showed a significant inverse correlation with their mRNA levels. Methylation levels were not associated with KCNJ5 or ATP1A1 mutations in human adrenal samples. We demonstrated an increased incidence of CpG island demethylation of GPCR-related gene in APA. The expression of two receptors, HTR4 and PTGER1, showed a strong association with DNA methylation. (C) 2017 Elsevier B.V. All rights reserved.