Abstract
Based on our previous studies and other evidence, miR-124 is an important biomarker and therapeutic target for major depressive disorder (MDD). The aim of this study was to clarify the role of miR-124 methylation in MDD and antidepressant effects from the perspective of epigenetics. MethylTarget™ was used to detect methylation levels of the three miR-124 precursor genes (MIR124-1, MIR124-2, and MIR124-3) in 33 pre- and post-treatment MDD patients and 33 healthy controls. A total of 11 cytosine-phosphate-guanine (CpG) islands in the three miR-124 precursor genes, including 222 CpG sites, were detected. All CpG islands were hypomethylated in MDD patients when compared to healthy controls and seven CpG regions were still identified with a statistically significant difference after Bonferroni correction. In addition, 137 of 222 CpG sites were found a statistical difference between MDD patients and controls, and 40 CpG sites were still statistically significant after Bonferroni correction. After performing the LASSO regression model, seven biomarkers with differential methylation among 40 CpG sites were identified. Mean methylation score was lower in MDD patients (z = −5.84, p = 5.16E-9). The AUC value reached 0.917 (95% CI: 0.854–0.981) to discriminate MDD and controls. No changes in methylation of the three miR-124 precursor genes were found in MDD patients following antidepressant treatment. The methylation of miR-124 could be a promising diagnostic biomarker for MDD.
Highlights
MicroRNAs are a class of small non-coding RNAs about 20–22 nucleotides that regulate gene expression at the post-transcriptional level (Flynt and Lai, 2008). miRNAs are abundant in the nervous system and can regulate two-thirds of genes in the human brain (Krol et al, 2010)
We found that the expression level of miR-124 from peripheral blood mononuclear cells (PBMCs) in major depressive disorder (MDD) patients was significantly increased than those in healthy controls, and it was significantly reduced after 8 weeks of antidepressant treatment (He et al, 2016)
There were no significant differences in gender, age, and body mass index (BMI) between MDD patients and healthy controls
Summary
MicroRNAs (miRNAs) are a class of small non-coding RNAs about 20–22 nucleotides that regulate gene expression at the post-transcriptional level (Flynt and Lai, 2008). miRNAs are abundant in the nervous system and can regulate two-thirds of genes in the human brain (Krol et al, 2010). AMP-responsive element-binding protein 1 (CREB1) (Yang et al, 2020), specificity protein 1 (SP1), DNA damage-inducible transcript 4 (DDIT4) (Wang et al, 2018), AKT1 substrate 1 (AKT1S1), nuclear receptor subfamily 3 group C member 1 (NR3C1) (Roy et al, 2017), and mitogen-activated protein kinase 14 (MAPK14) (Liu et al, 2018) It regulated some critical pathways, such as the mammalian target of rapamycin (mTOR) (Wang et al, 2018), glucocorticoid receptor (Wang et al, 2017), and the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathways (Bahi et al, 2014). A recent review suggested that miR-124 was probably an important biomarker and therapeutic target for MDD (Dwivedi, 2017)
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