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. 2015 Mar 12;10(3):e0121975.
doi: 10.1371/journal.pone.0121975. eCollection 2015.

Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder

Yunqiang Wan  1 , Yuanhui Liu  1 , Xiaobin Wang  1 , Jiali Wu  1 , Kezhi Liu  2 , Jun Zhou  1 , Li Liu  1 , Chunxiang Zhang  3
Affiliations

Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder

Yunqiang Wan et al. PLoS One. .

Abstract

Major depression is a debilitating disease. To date, the development of biomarkers of major depressive disorder (MDD) remains a challenge. Recently, alterations in the expression of microRNAs (miRNAs) from post-mortem brain tissue and peripheral blood have been linked to MDD. The goals of this study were to detect the differential miRNAs in cerebrospinal fluid (CSF) and serum of MDD patients. First, the relative expression levels of 179 miRNAs (relative high levels in serum) were analyzed by miRNA PCR Panel in the CSF of MDD patients. Then, the differentially altered miRNAs from CSF were further assessed by qRT-PCR in the serum of the same patients. Finally, the serum differentially altered miRNAs were further validated by qRT-PCR in the serum of another MDD patients. The CSF-results indicated that 11 miRNAs in MDD patients were significantly higher than these in control subjects, and 5 miRNAs were significantly lower than these in control subjects. The serum-results from the same patients showed that 3 miRNAs (miR-221-3p, miR-34a-5p, and let-7d-3p) of the 11 miRNAs were significantly higher than these in control subjects, and 1 miRNA (miR-451a) of 5 miRNAs was significantly lower than these in control subjects. The up-regulation of miR-221-3p, miR-34a-5p, let-7d-3p and down-regulation of miR-451a was further validated in another 32 MDD patients. ROC analysis showed that the area under curve of let-7d-3p, miR-34a-5p, miR-221-3p and miR-451a was 0.94, 0.98, 0.97 and 0.94, with specificity of 90.48%, 95.24%, 90.48% and 90.48%, and sensitivity of 93.75%, 96.88%, 90.63% and 84.85%, respectively. In addition, target gene prediction found that the altered miRNAs are involved in affecting some important genes and pathway related to MDD. Our results suggested that differentially altered miRNAs in CSF might be involved in MDD, and serum miR-221-3p, miR-34a-5p, let-7d-3p, and miR-451a might be able to serve as biomarkers for MDD.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. miRNAs that are significantly up-or down-regulated in the CSF from MDD vs. control subjects.
Fig 2
Fig 2. miRNAs that are significantly up- or down-regulated in the serum from the same 6 MDD vs. control subjects.
C: control subjects; T: MDD patients; FC: fold change; **p<0.01 vs control.
Fig 3
Fig 3. miRNAs that are significantly up-or down-regulated in the serum from another 32 MDD vs. 21 control subjects.
C: control subjects, T: MDD patients; FC: fold change; **p<0.0001 vs control.
Fig 4
Fig 4. Receiver operating characteristics curve evaluation of serum microRNAs for the diagnosis of MDD.
Let-7d-3p (A), miR-34a-5p (B), miR-221-3p (C) and miR-451a (D). AUC: the area under curve.
See this image and copyright information in PMC

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