Aberration of miRNAs expression in leukocytes from sporadic amyotrophic lateral sclerosis
Open accessAbstract
BACKGROUND: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS). Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS. METHODS: We analyzed the expression profiles of 1733 human mature miRNAs using microarray technology in leukocytes obtained from 5 patients with sporadic ALS (SALS) and 5 healthy controls. An independent group of 83 SALS patients, 24 Parkinson's disease (PD) patients and 61 controls was used for validation by real-time polymerase chain reaction assay. Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. In addition, target genes and signaling information of validated differential expression miRNAs were predicted using Bioinformatics. RESULTS: Eleven miRNAs, including four over-expressed and seven under-expressed miRNAs detected in SALS patients compared to healthy controls were selected for validation. Four under-expressed microRNAs, including hsa-miR-183, hsa-miR-193b, hsa-miR-451, and hsa-miR-3935, were confirmed in validation stage by comparison of 83 SALS patients and 61 HCs. Moreover, we identified a miRNA panel (hsa-miR-183, hsa-miR-193b, hsa-miR-451, and hsa-miR-3935) having a high diagnostic accuracy of SALS (AUC 0.857 for the validation group). However, only hsa-miR-183 was significantly lower in SALS patients than that in PD patients and in HCs, while no differences were found between PD patients and HCs. By bioinformatics analysis, we obtained a large number of target genes and signaling information that are linked to neurodegeneration. CONCLUSION: This study provided evidence of abnormal miRNA expression patterns in the peripheral blood leukocytes of SALS patients. Leukocytes miRNAs provide a promising opportunity for detection of SALS. The specificity of under-expression of hsa-miR-183 in SALS needs to be confirmed by further miRNA studies on other neurodegenerative diseases.
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miR-193b-3p is downregulated in ALS patients.
“In this study, we tried to clarify whether miR-193b-3p, a downregulated miRNA in ALS patients reported in our previous study (Chen et al., 2016), involves in cell survival by targeting TSC1/mTOR signaling in autophagy (Figure 6).”
From Downregulation of MicroRNA-193b-3p Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells (2017) · cites this paper as Chen et al., 2016
The Discussion reports lower hsa-miR-193b expression in leukocytes from Chinese patients with sporadic ALS than in healthy controls. Our copy does not identify the measured miRNA as the specific 3p form, so it supports the downregulation finding but not that added specificity. (LLM, conf=0.84)
Experimental — accuracy not yet measuredmiR-193b-3p was downregulated in sporadic ALS patients and provided high diagnostic accuracy for sporadic ALS.
“We noted that miR-193b-3p was downregulated in sALS patients and provided high diagnostic accuracy for sALS (Chen et al., 2016).”
From Downregulation of MicroRNA-193b-3p Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells (2017) · cites this paper as Chen et al., 2016
The Discussion reports that hsa-miR-193b was downregulated in sporadic ALS patients relative to healthy controls. But the paper does not identify the measured form as miR-193b-3p, and its reported AUCs for miR-193b (0.713 in the Results and 0.62 in the Discussion) do not support describing its individual diagnostic accuracy as high. (LLM, conf=0.88)
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- Authors
- Chen, Y., Wei, Q., Chen, X., Li, C., Cao, B., Ou, R., Hadano, S., & Shang, H.-F.
- Affiliations
- Sichuan University (CN)
- Tokai University (JP)
- Venue
- Frontiers in Molecular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2016-08-17
- Volume
- 9
- Pages
- 69-69
- ISSN
- 1662-5099 (ISSN-L)
- PMC
- PMC4987348
- OpenAlex
- W2510868781
- Cited by
- 69
- References
- 67
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 6 · 2019: 6 · 2018: 12 · 2017: 3
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (26290018)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- amyotrophic lateral sclerosis, sporadic ALS, microRNA expression, leukocytes, peripheral blood biomarkers, miRNA panel, Parkinson's disease, neurodegeneration, differential gene expression
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