Discovery of novel microRNAs and their pathogenic responsive target genes in mild traumatic brain injury

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.

Keywords: Cerebral cortex; Microrna; Mild traumatic brain injury; RNA sequencing; Target genes; q-RT-PCR.