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Published on: September 11, 2017
Discovery of novel microRNAs and their pathogenic responsive target genes in mild traumatic brain injury
Saurav Bhowmick1, M R Preetha Rani1, Shubham Singh1
1Laboratory of CNS Injury and Molecular Therapy, JFK Neuroscience Institute, Hackensack Meridian Health JFK University Medical Center, 65 James St, Edison, NJ, 08820, USA.
Abstract:
MicroRNAs (miRNAs) are non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. They are profound mediators of molecular and cellular changes in several pathophysiological conditions. Since miRNAs play major roles in regulating gene expression after traumatic brain injury (TBI), their possible role in diagnosis, prognosis, and therapy is not much explored. In this study, we aimed to identify specific miRNAs that are involved in the pathophysiological conditions in the first 24 h after mild TBI (mTBI). The genome-wide expression of miRNAs was evaluated by applying RNA sequence in the injury area of the cerebral cortex 24 after inflicting the injury using a mouse model of mild fluid percussion injury (FPI; 10 psi). Here, we identified different annotated, conserved, and novel miRNAs. A total of 978 miRNAs after 24 h of TBI were identified, and among these, 906 miRNAs were differentially expressed between control and mTBI groups. In this study, 146 miRNAs were identified as novel to mTBI and among them, 21 miRNAs were significant (p < 0.05). Using q-RT-PCR, we validated 10 differentially and significantly expressed novel miRNAs. Further, we filtered the differentially expressed miRNAs that were linked with proinflammatory cytokines, apoptosis, matrix metalloproteinases (MMPs), and tight junction and junctional adhesion molecule genes. Overall, this work shows that mTBI induces widespread changes in the expression of miRNAs that may underlie the progression of the TBI pathophysiology. The detection of several novel TBI-responsive miRNAs and their solid link with pathophysiological genes may help in identifying novel therapeutic targets.
Insights
Researchers identified novel microRNAs (miRNAs) responding to mild traumatic brain injury (mTBI) within 24 hours. These findings link specific miRNAs to TBI pathophysiology and suggest potential new therapeutic targets for brain injury.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression involved in various pathophysiological conditions.
- Their specific roles in the early stages of traumatic brain injury (TBI) remain underexplored, limiting diagnostic and therapeutic potential.
- Understanding early miRNA changes post-TBI is crucial for developing targeted interventions.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) involved in the pathophysiology of mild traumatic brain injury (mTBI) within the first 24 hours.
- To explore the potential of these miRNAs as diagnostic or therapeutic targets for mTBI.
- To investigate the link between differentially expressed miRNAs and key TBI-related genes.
Main Methods:
- Genome-wide miRNA expression profiling using RNA sequencing in a mouse model of mild fluid percussion injury (FPI).
- Analysis of miRNA expression in the cerebral cortex 24 hours post-injury.
- Validation of novel, differentially expressed miRNAs using quantitative reverse transcription polymerase chain reaction (q-RT-PCR).
Main Results:
- A total of 978 miRNAs were identified 24 hours after mTBI, with 906 showing differential expression compared to controls.
- 146 novel miRNAs were identified in response to mTBI, with 21 found to be statistically significant.
- Validated 10 novel, significantly differentially expressed miRNAs linked to genes involved in inflammation, apoptosis, matrix metalloproteinases, and cell adhesion.
Conclusions:
- Mild TBI induces widespread changes in miRNA expression within 24 hours.
- Novel TBI-responsive miRNAs identified in this study are associated with key pathophysiological pathways.
- These findings highlight potential novel therapeutic targets for managing mTBI progression.
