This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research Article
hairul islam Mohamed ibrahim
king faisal university
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved human subjects.
- The author confirmed that all appropriate ethical guidelines for the use of human subjects have been followed, any necessary IRB and/or ethics committee review has been obtained, and information about the IRB/ethics committee is included in the manuscript.
- The author has confirmed that all necessary patient/participant consent or assent has been obtained and the appropriate institutional forms have been archived. If the IRB/ethics committee waived the requirement for patient/participant consent or assent, an explanation for the waiver is included in the text.
- This study involved the use of non-human vertebrates.
- The author has confirmed that all appropriate ethical guidelines for the handling and use of animals in research have been followed and details of the oversight board have been included in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
The short non-coding microRNAs (miRNAs), have emerged as reliable modulators of various pathological conditions including autoimmune diseases in mammals. The current study, aims to identify new potential differential expressed miRNAs and their downstream mRNA targets of the autoimmune disease, Multiple sclerosis (MS). First, we used a computational tool to identify a new set of miRNA(s) that are probably implicated in MS. Preliminary, computational screening reveals that miR-659-3p, miR-659-5p, miR- 684, miR-3607-3p, miR-3607-5p, miR-3682-3p, miR-3682-5p miR-4647, miR-7188-3p, miR-7188-5p and miR-7235 are specifically elevated in the secondary lymphoid cells of EAE mice. In addition, expression of the downstream target genes of these miRNAs such as FXBO33, SGMS-1, ZDHHC-9, GABRA-3, NRXN-2 were reciprocal to miRNA expression in lymphoid cells. These confirmed by applying the mimic and silencing miRNA models, these data suggesting new inflammatory target genes of these promising miRNA biomarkers. The in vivo adoptive transfer model revealed that the suppression of miRNA-7188-5p and miR-7235 changed the pattern of astrocytes and CNSpathophysiology. The current study identified set of miRNAs and their mRNA targets as reciprocal regulator in MS disease. The absence of miRNA-7188-5p and miR-7235 enhanced the disease alleviation. These optimized results highlight new set of miRNA’s based biomarkers with therapeutic potential in experimental MS.
Keywords
Multiple sclerosis, experimental autoimmune encephalomyelitis, Micro-RNA, Therapeutic biomarkers
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
The full text of this article is available to read as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
- FigS1.tif
Supplementary S1. EAE induction and pathological validation. The evaluation of different miRNAs in isolated splenocytes using quantitative real time PCR and normalized by U6 controls. (A) EAE clinical score (B) Incidence of disease assessed for 24 days after immunization of EAE mice, n=8 mice. (C) miRNA profile was estimated in splenocytes of EAE mice after 24 days MOG immunization. (D, E). Histopathology of cervical spinal cord using hematoxylin and eosin staining at 200X magnification power. (F, G) Validation of demyelination in EAE mice using laxol fast blue staining and demyelination was quantified. Statistical data revealed the microscopic score of histochemical slides showed damage glial cells and astrocytes as well as lateral modification observed in the slides.
- FigS2..tif
Supplementary S2. Sequence match of miRNA and targeted 3’ UTR regions. The mature miRNA of miR-7188-3p and miR-7188-5p were binding match of 3’ UTR of MAPK-6 and GABRA-3 gene targets respectively. The miR-7235 showed binding match on 3’ UTR of NRXN-2 gene targets. miR-4647 showed binding match on 3’ UTR of FBXO-33. miR-684 showed binding matched sequence of 3’ UTR of SGMS-1 gene targets.
- graphical11.jpg
Schematic representation of Graphical abstract
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 29 Jan, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular & Molecular Neuroscience
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
hairul islam Mohamed ibrahim
king faisal university
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 29 Jan, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular & Molecular Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved human subjects.
- The author confirmed that all appropriate ethical guidelines for the use of human subjects have been followed, any necessary IRB and/or ethics committee review has been obtained, and information about the IRB/ethics committee is included in the manuscript.
- The author has confirmed that all necessary patient/participant consent or assent has been obtained and the appropriate institutional forms have been archived. If the IRB/ethics committee waived the requirement for patient/participant consent or assent, an explanation for the waiver is included in the text.
- This study involved the use of non-human vertebrates.
- The author has confirmed that all appropriate ethical guidelines for the handling and use of animals in research have been followed and details of the oversight board have been included in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
The short non-coding microRNAs (miRNAs), have emerged as reliable modulators of various pathological conditions including autoimmune diseases in mammals. The current study, aims to identify new potential differential expressed miRNAs and their downstream mRNA targets of the autoimmune disease, Multiple sclerosis (MS). First, we used a computational tool to identify a new set of miRNA(s) that are probably implicated in MS. Preliminary, computational screening reveals that miR-659-3p, miR-659-5p, miR- 684, miR-3607-3p, miR-3607-5p, miR-3682-3p, miR-3682-5p miR-4647, miR-7188-3p, miR-7188-5p and miR-7235 are specifically elevated in the secondary lymphoid cells of EAE mice. In addition, expression of the downstream target genes of these miRNAs such as FXBO33, SGMS-1, ZDHHC-9, GABRA-3, NRXN-2 were reciprocal to miRNA expression in lymphoid cells. These confirmed by applying the mimic and silencing miRNA models, these data suggesting new inflammatory target genes of these promising miRNA biomarkers. The in vivo adoptive transfer model revealed that the suppression of miRNA-7188-5p and miR-7235 changed the pattern of astrocytes and CNSpathophysiology. The current study identified set of miRNAs and their mRNA targets as reciprocal regulator in MS disease. The absence of miRNA-7188-5p and miR-7235 enhanced the disease alleviation. These optimized results highlight new set of miRNA’s based biomarkers with therapeutic potential in experimental MS.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
The full text of this article is available to read as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
- FigS1.tif
Supplementary S1. EAE induction and pathological validation. The evaluation of different miRNAs in isolated splenocytes using quantitative real time PCR and normalized by U6 controls. (A) EAE clinical score (B) Incidence of disease assessed for 24 days after immunization of EAE mice, n=8 mice. (C) miRNA profile was estimated in splenocytes of EAE mice after 24 days MOG immunization. (D, E). Histopathology of cervical spinal cord using hematoxylin and eosin staining at 200X magnification power. (F, G) Validation of demyelination in EAE mice using laxol fast blue staining and demyelination was quantified. Statistical data revealed the microscopic score of histochemical slides showed damage glial cells and astrocytes as well as lateral modification observed in the slides.
- FigS2..tif
Supplementary S2. Sequence match of miRNA and targeted 3’ UTR regions. The mature miRNA of miR-7188-3p and miR-7188-5p were binding match of 3’ UTR of MAPK-6 and GABRA-3 gene targets respectively. The miR-7235 showed binding match on 3’ UTR of NRXN-2 gene targets. miR-4647 showed binding match on 3’ UTR of FBXO-33. miR-684 showed binding matched sequence of 3’ UTR of SGMS-1 gene targets.
- graphical11.jpg
Schematic representation of Graphical abstract
Loading...