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Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis.
Front Mol Neurosci. 2016; 9:69.FM

Abstract

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.

Authors+Show Affiliations

Department of Neurology, West China Hospital, Sichuan University Chengdu, China.Department of Neurology, West China Hospital, Sichuan University Chengdu, China.Department of Neurology, West China Hospital, Sichuan University Chengdu, China.Department of Neurology, West China Hospital, Sichuan University Chengdu, China.Department of Neurology, West China Hospital, Sichuan University Chengdu, China.Department of Neurology, West China Hospital, Sichuan University Chengdu, China.Department of Molecular Life Sciences, Tokai University School of MedicineIsehara, Japan; The Institute of Medical Sciences, Tokai UniversityIsehara, Japan; Research Center for Brain and Nervous Diseases, Tokai University Graduate School of MedicineIsehara, Japan.Department of Neurology, West China Hospital, Sichuan University Chengdu, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27582688

Citation

Chen, YongPing, et al. "Aberration of miRNAs Expression in Leukocytes From Sporadic Amyotrophic Lateral Sclerosis." Frontiers in Molecular Neuroscience, vol. 9, 2016, p. 69.
Chen Y, Wei Q, Chen X, et al. Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis. Front Mol Neurosci. 2016;9:69.
Chen, Y., Wei, Q., Chen, X., Li, C., Cao, B., Ou, R., Hadano, S., & Shang, H. F. (2016). Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis. Frontiers in Molecular Neuroscience, 9, 69. https://doi.org/10.3389/fnmol.2016.00069
Chen Y, et al. Aberration of miRNAs Expression in Leukocytes From Sporadic Amyotrophic Lateral Sclerosis. Front Mol Neurosci. 2016;9:69. PubMed PMID: 27582688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis. AU - Chen,YongPing, AU - Wei,QianQian, AU - Chen,XuePing, AU - Li,ChunYu, AU - Cao,Bei, AU - Ou,RuWei, AU - Hadano,Shinji, AU - Shang,Hui-Fang, Y1 - 2016/08/17/ PY - 2016/07/02/received PY - 2016/07/29/accepted PY - 2016/9/2/entrez PY - 2016/9/2/pubmed PY - 2016/9/2/medline KW - amyotrophic lateral sclerosis KW - biomarker KW - hsa-miR-183 KW - miRNAs KW - microarray KW - pathway SP - 69 EP - 69 JF - Frontiers in molecular neuroscience JO - Front Mol Neurosci VL - 9 N2 - 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. SN - 1662-5099 UR - https://www.unboundmedicine.com/medline/citation/27582688/Aberration_of_miRNAs_Expression_in_Leukocytes_from_Sporadic_Amyotrophic_Lateral_Sclerosis_ DB - PRIME DP - Unbound Medicine ER -
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