Non-coding RNAs as key player in stem cell proliferation anddifferentiation; Potential therapeutic strategies in spinal cord injuries
Shaimaa MohamedMarwa MatboliAyman ShafeiHossam KhalafMohamed AshrafMohamed S. RiadBadr MuhammadMahmoud Abd El-gawadMohab DeyabIslam Ramadan Mahmoud A. Ali
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Spinal cord injury (SCI) is a devastating condition which often results in the loss of sensory and motor function below the lesion site. The consequences of SCI constitute substantial burden to both the patient and society. Existing treatments for SCI injuries have proved inadequate, partly owing to an incomplete understanding of post-injury cellular and molecular changes. SCI triggers a multitude of pathophysiological events that are tightly regulated by the expression levels of specific genes. It has been shown that numerous non coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are differentially expressed following SCI. MiRNA and lncRNA could, as regulators of gene expression at the post-transcriptional level, affect the pathophysiology of SCI. In addition, these ncRNAs are emerging as key regulators of stem cell differentiation and proliferation, thus, manipulating their levels could improve future therapeutic neural stem cell transplantation strategies. This review will discuss the most common and well-established therapeutic strategies (specially focusing on stem cell and non-coding RNAs studies) in SCI managementCite
Background and purpose: Spinal cord injury (SCI) involves serious damage that can result in abnormal or absent motor and sensory functions and a disruption of autonomic function, and a series of pathological reactions occur after the injury. As a type of small non-coding RNA, microRNAs (miRNAs) have been verified to inhibit gene expression via post-transcriptional regulation. This review mainly focuses on recent advances regarding the roles of miRNAs following SCI. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. The studies regarding the roles of miRNAs following SCI were identified through PubMed, Embase and Web of Science. We summarise the changes in expression levels of miRNAs and discuss the roles of miRNAs after SCI. Results: A total of 77 empirical studies meeting the inclusion criteria were identified. Existing studies showed that miRNAs were temporally altered and had effects on apoptosis, inflammation, angiogenesis, astrogliosis, oligodendrocyte development, axonal regeneration and remyelination after SCI. The alteration of miRNAs and the regulative action of pathological reactions can also provide opportunities for potential therapeutic interventions. "miRNA replacement therapy" aims to transfer miRNAs into diseased cells via delivery techniques and improve targeting effectiveness in cells, and this novel therapeutic tool provides a promising technique to promote the repair of SCI and reduces functional deficits. Conclusions: This review is helpful for understanding the underlying mechanisms of SCI and the potential clinical value of miRNAs. miRNAs have the potential to be attractive tools and targets for novel diagnostic and therapeutic approaches of SCI.
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Spinal cord injury (SCI) is a highly debilitating disease and is increasingly being recognized as an important global health priority. However, the mechanisms underlying SCI have not yet been fully elucidated, and effective therapies for SCI are lacking. Long noncoding RNAs (lncRNAs), which form a major class of noncoding RNAs, have emerged as novel targets for regulating several physiological functions and mediating numerous neurological diseases. Notably, gene expression profile analyses have demonstrated aberrant changes in lncRNA expression in rats or mice after traumatic or nontraumatic SCI. LncRNAs have been shown to be associated with multiple pathophysiological processes following SCI including inflammation, neural apoptosis, and oxidative stress. They also play a crucial role in the complications associated with SCI, such as neuropathic pain. At the same time, some lncRNAs have been found to be therapeutic targets for neural stem cell transplantation and hydrogen sulfide treatment aimed at alleviating SCI. Therefore, lncRNAs could be promising biomarkers for the diagnosis, treatment, and prognosis of SCI. However, further researches are required to clarify the therapeutic effects of lncRNAs on SCI and the mechanisms underlying these effects. In this study, we reviewed the current progress of the studies on the involvement of lncRNAs in SCI, with the aim of drawing attention towards their roles in this debilitating condition.
MEG3
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Trauma to the spinal cord causes permanent disability to more than 180,000 people every year worldwide. The initial mechanical damage triggers a complex set of secondary events involving the neural, vascular, and immune systems that largely determine the functional outcome of the spinal cord injury (SCI). Cellular and biochemical mechanisms responsible for this secondary injury largely depend on activation and inactivation of specific gene programs. Recent studies indicate that microRNAs function as gene expression switches in key processes of the SCI. Microarray data from rodent contusion models reveal that SCI induces changes in the global microRNA expression patterns. Variations in microRNA abundance largely result from alterations in the expression of the cells at the damaged spinal cord. However, microRNA expression levels after SCI are also influenced by the infiltration of immune cells to the injury site and the death and migration of specific neural cells after injury. Evidences on the role of microRNAs in the SCI pathophysiology have come from different sources. Bioinformatic analysis of microarray data has been used to identify specific variations in microRNA expression underlying transcriptional changes in target genes, which are involved in key processes in the SCI. Direct evidences on the role of microRNAs in SCI are scarcer, although recent studies have identified several microRNAs (miR-21, miR/486, miR-20) involved in key mechanisms of the SCI such as cell death or astrogliosis, among others. From a clinical perspective, different evidences make clear that microRNAs can be potent therapeutic tools to manipulate cell state and molecular processes in order to enhance functional recovery. The present article reviews the actual knowledge on how injury affects microRNA expression and the meaning of these changes in the SCI pathophysiology, to finally explore the clinical potential of microRNAs in the SCI.
Astrogliosis
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MicroRNAs are a class of recently discovered, small non-coding RNAs that have been shown to play essential roles in a vast majority of biological processes. Very little is known about the role of microRNAs during spinal cord injury. This review summarizes the changes in expression levels of microRNAs after spinal cord injury. These aberrant changes suggest that microRNAs play an important role in inflammation, oxidative stress, apoptosis, glial scar formation and axonal regeneration. Given their small size and specificity of action, microRNAs could be potential therapeutics for treating spinal cord injury in the future. There are rapidly developing techniques for manipulating microRNA levels in animals; we review different chemical modification and delivery strategies. These may provide platforms for designing efficient microRNA delivery protocols for use in the clinic.
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Spinal cord injury (SCI) is a severe CNS injury that results in abnormalities in, or loss of, motor, sensory and autonomic nervous function. miRNAs belong to a new class of noncoding RNA that regulates the production of proteins and biological function of cells by silencing translation or interfering with the expression of target mRNAs. Following SCI, miRNAs related to oxidative stress, inflammation, autophagy, apoptosis and many other secondary injuries are differentially expressed, and these miRNAs play an important role in the progression of secondary injuries after SCI. The purpose of this review is to elucidate the differential expression and functional roles of miRNAs after SCI, thus providing references for further research on miRNAs in SCI.
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microRNAs (miRNAs) are a novel class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level.miRNAs can modulate gene expression and thus play important roles in diverse neurobiological processes, such as cell differentiation, growth, proliferation and neural activity, as well as the pathogenic processes of spinal cord injury (SCI) like inflammation, oxidation, demyelination and apoptosis.Results from animal studies have revealed the temporal alterations in the expression of a large set of miRNAs following SCI in adult rats, and the expressional changes in miRNAs following SCI is bidirectional (increase or decrease).In addition, several miRNAs have distinct roles in prognosis of SCI (protective, detrimental and varied).Taken together, the existing evidence suggests that abnormal miRNA expression following SCI contributes to the pathogenesis of SCI, and miRNAs may become potential targets for the therapy of SCI.
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