Promoter Hypomethylation of miR-124 Gene Is Associated With Major Depressive Disorder

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.

Integrated Module of Multidimensional Omics for Peripheral Biomarkers (iMORE) in patients with major depressive disorder: rationale and design of a prospective multicentre cohort study

“…Our previous research also supported metabolomics has potential in biomarkers exploration related to the diagnosis and treatment of mental disorders 47 48. In addition, emerging fields, known as epigenomics and microbiome, have shown some degree of association with prognosis 49–52…”

“…47 48 In addition, emerging fields, known as epigenomics and microbiome, have shown some degree of association with prognosis. [49][50][51][52] Current studies of gut microbiota-brain axis and neuroimmunology suggest a need for integrated analysis. Decreased faecal microbiota richness and diversity were observed in some MDD studies and associated with altered serum metabolites and decreased immunoglobulin.…”

Dissecting early life stress-induced adolescent depression through epigenomic approach

“…In the past few years, a considerable amount of research has been conducted to examine the role of miRNAs in neuropsychiatric disease [147][148][149][150][151][152][153][154][155][156]. We and other investigators have examined the expression of miRNAs in human postmortem brains of depressed subjects, in the brain of animals showing depression-like behavior, and in peripheral tissues such as blood, urine, and saliva [6,96,144,150,[157][158][159][160][161][162][163][164][165][166][167]. We have demonstrated that miRNAs form highly correlated networks in the brains of MDD subjects that differ from healthy controls, suggesting that miRNA networks can give rise to specific behavioral phenotypes [96,168,169].…”

M6A RNA Methylation-Based Epitranscriptomic Modifications in Plasticity-Related Genes via miR-124-C/EBPα-FTO-Transcriptional Axis in the Hippocampus of Learned Helplessness Rats

“…Our findings of the involvement of miR-124 in regulating the FTO gene via transcription factor C/EBP-α are highly relevant. We and other investigators have shown that miR-124-3p plays a crucial role in synaptic plasticity and stress-related disorders ( Sun et al, 2015 ; Dwivedi, 2017 ; Roy et al, 2017a ; Gu et al, 2019 ; Yang et al, 2020 ; Zeng et al, 2021 ). Knockdown of miR-124 reduces depression-like behavior in chronic unpredictable stress–induced depressive rats ( Yang et al, 2020 ).…”