Identification of Differential MicroRNAs in Cerebrospinal Fluid and Serum of Patients with Major Depressive Disorder
Open accessAbstract
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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Wan et al. reported that 16 miRNAs were significantly up- or down-regulated in the CSF of patients with major depressive disorder compared to healthy controls.
“For example, Wan et al. recently reported that 16 miRNAs were significantly up- or down-regulated in the CSF of patients with major depressive disorder compared to healthy controls40.”
From Intra- and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery (2017) · cites this paper as [40]
The Results section reports 16 significantly altered CSF miRNAs in six patients with major depressive disorder compared with six controls: 11 were higher and five lower. However, the Patient characteristics section says the CSF controls had renal calculi or bladder stones; the healthy individuals belonged to the separate serum-validation group. Calling the CSF controls healthy overstates the source. (LLM, conf=0.91)
Experimental — accuracy not yet measuredAmong the down-regulated miRNAs in the patients, miR-451a was significantly decreased, with a fold change of 8.7.
“Among the down-regulated miRNAs in the patients, miR-451a was significantly decreased, with a fold change of 8.7.”
From Intra- and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery (2017) · cites this paper as [40]
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- Authors
- Wan, Y., Liu, Y., Wang, X., Wu, J., Liu, K., Zhou, J., Liu, L., & Zhang, C.
- Affiliations
- Southwest Medical University (CN)
- Rush University (US)
- Corresponding author
- Wang, Xiaobin
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-03-12
- Volume
- 10
- Issue
- 3
- Pages
- e0121975
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4357380
- OpenAlex
- W1965831320
- Cited by
- 182
- References
- 4
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 17 · 2023: 14 · 2022: 20 · 2021: 25 · 2020: 13 · 2019: 14 · 2018: 18 · 2017: 18 · 2016: 19 · 2015: 3 · 2014: 1
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81271478)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, microRNA, cerebrospinal fluid, serum biomarkers, miR-221-3p, miR-34a-5p, miR-451a, differentially expressed miRNAs, diagnostic biomarkers, miRNA target prediction, peripheral blood biomarkers
- MeSH terms
- Adult, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Prognosis, Biomarkers, MicroRNAs, Young Adult
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