Association of DNA methylation with steroidogenic enzymes in Cushing’s adenoma

Abstract

DNA methylation and demethylation regulate the transcription of genes. DNA methylation-associated gene expression of adrenal steroidogenic enzymes may regulate cortisol production in cortisol-producing adenoma (CPA). We aimed to determine the DNA methylation levels of all genes encoding steroidogenic enzymes involved in CPA. Additionally, the aims were to clarify the DNA methylation-associated gene expression and evaluate the difference of CPA genotype from others using DNA methylation data. Twenty-five adrenal CPA and six nonfunctioning adrenocortical adenoma (NFA) samples were analyzed. RNA sequencing and DNA methylation array were performed. The methylation levels at 118 methylation sites of the genes were investigated, and their methylation and mRNA levels were subsequently integrated. Among all the steroidogenic enzyme genes studied, CYP17A1 gene was mainly found to be hypomethylated in CPA compared to that in NFA, and the Benjamini-Hochberg procedure demonstrated that methylation levels at two sites in the CYP17A1 gene body were statistically significant. PRKACA mutant CPAs predominantly exhibited hypomethylation of CYP17A1 gene compared with the GNAS mutant CPAs. Inverse associations between CYP17A1 methylation in three regions of the gene body and its mRNA levels were observed in the NFAs and CPAs. In applying clustering analysis using CYP17A1 methylation and mRNA levels, CPAs with PRKACA mutation were differentiated from NFAs and CPAs with a GNAS mutation. We demonstrated that CPAs exhibited hypomethylation of the CYP17A1 gene body in CPA, especially in the PRKACA mutant CPAs. Methylation of CYP17A1 gene may influence its transcription levels.

Integrated transcriptome, proteome and single‐cell sequencing uncover the prognostic and immunological features of colony‐stimulating factor 3 receptor in pan‐cancer

“…The gene silencing caused by aberrant promoter methylation has been demonstrated in oncogenesis and progression, which showed the potential as a prognostic or therapeutic biomarker. [25][26][27] The present study identified that the promoter methylation levels of CSF3R…”

Hypermethylation of tumor suppressor lncRNA MEF2C-AS1 frequently happened in patients at all stages of colorectal carcinogenesis

“…It is noteworthy that promoter methylation plays an important regulatory role in gene expression [30][31][32]. Although previous studies have reported that MEF2C-AS1 was downregulated in DGC [27] and CC [28] lesion tissues, and BC [29] cells, the current study is the first that systematically described the MEF2C-AS1 methylation status and its influence on expression.…”