The role of long noncoding RNA in traumatic brain injury

Abstract

Traumatic brain injury (TBI), a mainly lethal and highly debilitating condition, is increasing worldwide. However, the underlying mechanism has not been fully elucidated and effective therapy is needed. Long noncoding RNAs (lncRNAs), which form a major class of noncoding RNAs, have emerged as novel targets for regulating physiological functions and mediating numerous neurological diseases. Notably, gene expression profile analyses have demonstrated aberrant changes in lncRNA expression in the cerebral cortex and hippocampus of rats, mice and human after TBI. lncRNAs may be associated with multiple pathophysiological processes following TBI and might play a crucial role in complications of TBI, such as traumatic optic neuropathy due to the regulation of specific signaling pathways. Some lncRNAs have also been found to be therapeutic targets for motor and cognitive recovery after TBI. lncRNAs may be promising biomarkers for TBI diagnosis, treatment, and prognosis prediction. However, further research isneeded to clarify the underlying mechanisms and therapeutic effects of lncRNAs on TBI. We review the current progress of studies on lncRNAs in TBI to draw more attention to their roles in this debilitating condition.

Keywords: long non-coding RNA; neuropathy; traumatic brain injury.

Figure 1

The probable mechanisms of the effects produced by lncRNAs on TBI. Notes: There are several lncRNAs that have been reported to play different roles in the process of TBI. Knocking down GAS5 would alleviate RGCs oxidative stress injury by upregulating miR-124. GAS5 could also inhibit microglia M2 polarization by suppressing transcription of TRF4. lincRNA-p21 may promote microglial activation through a p53-dependent transcriptional pathway. In addition to neuroinflammation, lncRNA MALAT1 is also related to neurodegeneration and astrocyte apoptosis via CREB signaling pathway and alternative splicing of PKC δII respectively. Astrocyte apoptosis are associated with NEAT1 and Gm4419 in which Gm4419 could play the role of sponge for miR-466l which could target TNF-α. H19 is considered to alleviate hypoxia-induced injury by downregulated miR-28 expression. SNHG1 protected secondary cerebral ischemia and hypoxia via sponging miR-338. Abbreviations: lncRNA, long noncoding RNA; TBI, traumatic brain injury; GAS5, growth arrest-specific 5; RGC, retinal ganglion cells; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; CREB, cAMP response element-binding protein; NEAT1, nuclear enriched abundant transcript 1; TNF-α, tumor necrosis factor-alpha; SNHG1, small nucleolar RNA host gene 1.