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Published on: August 3, 2018
Dysregulation of miR-193a serves as a potential contributor to MS pathogenesis via affecting RhoA and Rock1
Nasim Saeidi1, Hadi Goudarzvand2, Hamed Mohammadi3
1DNA Laboratory, Analytical Laboratories, Hamilton, New Zealand.
Background:
Multiple sclerosis (MS) is one of the most common neurological diseases that cause chronic inflammation of the central nervous system and demyelination of the myelin sheath. At present, microRNAs (miRNAs) are considered not only a diagnostic and prognostic indicator of diseases but also a new goal in gene therapy. This study aims to find a simple, non-invasive, valuable biomarker for early detection and potential treatment of MS.
Methods:
In the present study, 30 patients with MS were included. The qRT-PCR method was performed to evaluate the expression level of miR-193a, RhoA, and ROCK1. Besides, western blotting was performed to determine the expression level of RhoA and ROCK1 at protein levels. Moreover, we aimed to clarify the possible correlation between miR-193a-5p and its-regulated target genes so that miR-193a-5p mimic was transfected into MS-derived cultured PBMSs, and the expression level of RhoA and ROCK1 were then evaluated by qRT-PCR and Western blotting. In the final step, the correlation between miR-193a-5p and clinicopathological features of patients was investigated.
Results:
Results showed that miR-193a was decreased while RhoA and ROCK1 were up-regulated in PBMCs obtained from patients with MS compared to the control group. It was also revealed that miR-193a transfection reduced RhoA and ROCK1 expression at mRNA and protein levels. The results from the Chi-square analysis showed that down-regulation of miR-193a was associated with increased CRP level, CSF IgG positivity, and MSSS (Multiple Sclerosis Severity Score), suggesting miR-193a is a potential diagnostic and prognostic indicator.
Conclusion:
We implied that miR-193a could modulate RhoA and ROCK 1 expression in MS patients, in which its down-regulation leads to increased expression of RhoA and ROCK1 and poor prognosis of patients with MS. Therefore, miR-193a and its associated targets could serve potential prognostic, diagnostic, and therapeutic efficacy in MS patients.
Insights
Reduced miR-193a levels in multiple sclerosis (MS) patients correlate with increased RhoA and ROCK1 expression, indicating potential as a diagnostic and therapeutic biomarker for MS.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease.
- MicroRNAs (miRNAs) are key regulators and potential biomarkers for diseases.
- Identifying novel biomarkers for MS early detection and treatment is crucial.
Purpose of the Study:
- To investigate the role of miR-193a in multiple sclerosis (MS).
- To explore miR-193a as a potential diagnostic and prognostic biomarker for MS.
- To assess miR-193a's therapeutic potential in MS.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blotting were used to assess miR-193a, RhoA, and ROCK1 expression in MS patients.
- miR-193a mimic transfection was performed in MS-derived peripheral blood mononuclear cells (PBMCs).
- Correlation analysis between miR-193a levels and clinicopathological features was conducted.
Main Results:
- miR-193a expression was significantly decreased in MS patients' PBMCs compared to controls.
- RhoA and ROCK1 expression levels were elevated in MS patients and reduced upon miR-193a transfection.
- Down-regulation of miR-193a correlated with increased C-reactive protein (CRP), cerebrospinal fluid (CSF) IgG positivity, and Multiple Sclerosis Severity Score (MSSS).
Conclusions:
- miR-193a down-regulation modulates RhoA and ROCK1 expression in MS, contributing to disease progression.
- miR-193a and its targets (RhoA, ROCK1) show promise as diagnostic, prognostic, and therapeutic targets for MS.
- This study highlights miR-193a as a potential non-invasive biomarker for MS.
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