Role of regulatory non-coding RNAs in traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a potentially fatal health event that cannot be predicted in advance. After TBI occurs, it can have enduring consequences within both familial and social spheres. Yet, despite extensive efforts to improve medical interventions and tailor healthcare services, TBI still remains a major contributor to global disability and mortality rates. The prompt and accurate diagnosis of TBI in clinical contexts, coupled with the implementation of effective therapeutic strategies, remains an arduous challenge. However, a deeper understanding of changes in gene expression and the underlying molecular regulatory processes may alleviate this pressing issue. In recent years, the study of regulatory non-coding RNAs (ncRNAs), a diverse class of RNA molecules with regulatory functions, has been a potential game changer in TBI research. Notably, the identification of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs has revealed their potential as novel diagnostic biomarkers and therapeutic targets for TBI, owing to their ability to regulate the expression of numerous genes. In this review, we seek to provide a comprehensive overview of the functions of regulatory ncRNAs in TBI. We also summarize regulatory ncRNAs used for treatment in animal models, as well as miRNAs, lncRNAs, and circRNAs that served as biomarkers for TBI diagnosis and prognosis. Finally, we discuss future challenges and prospects in diagnosing and treating TBI patients in the clinical settings.

Keywords: Biomarkers; Brain trauma; Circular RNAs; Long non-coding RNAs; MicroRNAs; Therapeutic target.

Figure 1.. The role of regulatory ncRNAs after TBI in humans and animal models.

Multifaceted role and mechanisms of ncRNAs in TBI include neuroinflammation, white matter damage, neuron death, brain edema and microvascular injury. (A) Within TBI, regulatory ncRNAs are involved in the neuroinflammation process mainly including the polarization of microglia/macrophage and the activated astrocytes. Neuroinflammation can lead to neuron damage and neurological deficits. (B) Regulatory ncRNAs contribute to brain white matter injury following TBI. (C) Regulatory ncRNAs are involved in the pathological process of neuron death after TBI. Neuron death including apoptosis, autophagy, and ferroptosis has been detected in the injured brain area. (D) Regulatory ncRNAs are involved in brain edema and microvascular damage after TBI. Created with BioRender.com.

Figure 2.. The different sources of regulatory ncRNAs as biomarkers for TBI patients.

Various regulatory ncRNAs including miRNAs, lncRNAs, circRNAs, and snoRNAs have been identified as diagnostic and prognosis biomarkers for TBI patients. Currently, the sources of regulatory ncRNAs are mainly from saliva, CSF, serum, plasma, and peripheral blood mononuclear cells. “↑”, represents increased expression level of regulatory ncRNAs in patients after TBI. “↓”, represents decreased expression level of regulatory ncRNAs in patients after TBI. MiRNAs with “*”, represent increased expression levels in patients with mTBI but decreased expression levels in patients with sTBI. Created with BioRender.com.