Role of Non-coding RNAs in Axon Regeneration after Peripheral Nerve Injury

Peripheral nerve injury (PNI) may lead to disability and neuropathic pain, which constitutes a substantial economic burden to patients and society. It was found that the peripheral nervous system (PNS) has the ability to regenerate after injury due to a permissive microenvironment mainly provided by Schwann cells (SCs) and the intrinsic growth capacity of neurons; however, the results of injury repair are not always satisfactory. Effective, long-distance axon regeneration after PNI is achieved by precise regulation of gene expression. Numerous studies have shown that in the process of peripheral nerve damage and repair, differential expression of non-coding RNAs (ncRNAs) significantly affects axon regeneration, especially expression of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). In the present article, we review the cellular and molecular mechanisms of axon regeneration after PNI, and analyze the roles of these ncRNAs in nerve repair. In addition, we discuss the characteristics and functions of these ncRNAs. Finally, we provide a thorough perspective on the functional mechanisms of ncRNAs in nervous injury repair, and explore the potential these ncRNAs offer as targets of nerve injury treatment.     

Unlocking the potential of non-coding RNAs in cancer research and therapy

Non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, with growing evidence implicating their involvement in cancer development and progression. The potential of ncRNAs as diagnostic and prognostic biomarkers for cancer is promising, with emphasis on their use in liquid biopsy and tissue-based diagnostics. In a nutshell, the review comprehensively summarizes the diverse classes of ncRNAs implicated in cancer, including microRNAs, long non-coding RNAs, and circular RNAs, and their functions and mechanisms of action. Furthermore, we describe the potential therapeutic applications of ncRNAs, including anti-miRNA oligonucleotides, siRNAs, and other RNA-based therapeutics in cancer treatment. However, significant challenges remain in developing effective ncRNA-based diagnostics and therapeutics, including the lack of specificity, limited understanding of mechanisms, and delivery challenges. This review also covers the current state-of-the-art non-coding RNA research technologies and bioinformatic analysis tools. Lastly, we outline future research directions in non-coding RNA research in cancer, including developing novel biomarkers, therapeutic targets, and modalities. In summary, this review provides a comprehensive understanding of non-coding RNAs in cancer and their potential clinical applications, highlighting both the opportunities and challenges in this rapidly evolving field.     

Clinical significance of the interaction between non-coding RNAs and the epigenetics machinery

Non-coding RNAs and epigenetics are remarkable mechanisms of cellular control. In this review we underline the processes by which non-coding RNAs (ncRNAs), shown to be involved in various diseases, are capable of modifying and being modified by the epigenetic machinery, emphasizing the clinical importance of this network in cancer. Many ncRNAs have been described that play important roles in the establishment and maintenance of the epigenome. However, only a few studies deeply take into account the role of ncRNAs from a clinicopathological standpoint. The wide range of interactions between the non-coding RNome and the epigenome, and the roles of these networks in the pathogenesis, prognosis and early diagnosis of many diseases, present new challenges and opportunities for future studies regarding therapeutic strategies in oncology.     

MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two relevant classes of non-coding RNAs (ncRNAs) that play a pivotal role in a number of molecular processes through different epigenetic regulatory mechanisms of gene expression. As a matter of fact, the altered expression of these types of RNAs leads to the development and progression of a varied range of multifactorial human diseases. Several recent reports elucidated that miRNA and lncRNAs have been implicated in pancreatic cancer (PC). For instance, dysregulation of such ncRNAs has been found to be associated with chemoresistance, apoptosis, autophagy, cell differentiation, tumor suppression, tumor growth, cancer cell proliferation, migration, and invasion in PC. Moreover, several aberrantly expressed miRNAs and lncRNAs have the potential to be used as biomarkers for accurate PC diagnosis. Additionally, miRNAs and lncRNAs are considered as promising clinical targets for PC. Therefore, in this review, we discuss recent experimental evidence regarding the clinical implications of miRNAs and lncRNAs in the pathophysiology of PC, their future potential, as well as the challenges that have arisen in this field of study in order to drive forward the design of ncRNA-based diagnostics and therapeutics for PC.     

Non-coding RNAs, epigenetics and complexity

Several aspects of epigenetics are strongly linked to non-coding RNAs, especially small RNAs that can direct the cytosine methylation and histone modifications that are implicated in gene expression regulation in complex organisms. A fundamental characteristic of epigenetics is that the same genome can show alternative phenotypes, which are based in different epigenetic states. Some of the most studied complex epigenetic phenomena including transposon activity and silencing recently exemplified by piRNAs (piwi-interacting RNAs), position effect variegation, X-chromosome inactivation, parental imprinting, and paramutation have direct or indirect participation of an RNA component. Conceivably, most of the non-coding RNAs with no described function yet, are players in epigenetic mechanisms that are still not completely understood. In that regard, RNAs were recently implicated in new mechanisms of genetic information transfer in yeast, plants and mice. In this review article, the hypothesis that non-coding RNAs might be the main component of complex organisms acquired during evolution will be explored. The question of how evolutionary theories have been challenged by these molecules in association with epigenetic mechanisms will also be discussed here.     

Monoallelic gene expression in mammals

Three systems of monoallelic gene expression in mammals are known, namely, X-chromosome inactivation, imprinting, and allelic exclusion. In all three systems, monoallelic expression is regulated epigenetically and is frequently directed by long non-coding RNAs (ncRNAs). This review briefs all three systems of monoallelic gene expression in mammals focusing on chromatin modifications, spatial chromosome organization in the nucleus, and the functioning of ncRNAs.     

表观遗传学: 生物细胞非编码RNA调控的研究进展

表观遗传学是研究基因表达发生了可遗传的改变, 而DNA序列不发生改变的一门生物学分支, 对细胞的生长分化及肿瘤的发生发展至关重要。表观遗传学的主要机制包括DNA甲基化、组蛋白修饰及新近发现的非编码RNA。非编码RNA 是指不能翻译为蛋白的功能性RNA分子, 其中常见的具调控作用的非编码RNA包括小干涉RNA、miRNA、piRNA 以及长链非编码RNA。近年来大量研究表明非编码RNA在表观遗传学的调控中扮演了越来越重要的角色。文章综述了近年来生物细胞非编码RNA调控的表观遗传学研究进展, 以有助于理解哺乳动物细胞中非编码RNA及其调控机制和功能。     

Long ncRNA expression associates with tissue-specific enhancers

Long non-coding RNAs (ncRNA) have recently been demonstrated to be expressed from a subset of enhancers and to be required for the distant regulation of gene expression. Several approaches to predict enhancers have been developed based on various chromatin marks and occupancy of enhancer-binding proteins. Despite the rapid advances in the field, no consensus how to define tissue specific enhancers yet exists. Here, we identify 2,695 long ncRNAs annotated by ENCODE (corresponding to 28% of all ENCODE annotated long ncRNAs) that overlap tissue-specific enhancers. We use a recently developed algorithm to predict tissue-specific enhancers, PreSTIGE, that is based on the H3K4me1 mark and tissue specific expression of mRNAs. The expression of the long ncRNAs overlapping enhancers is significantly higher when the enhancer is predicted as active in a specific cell line, suggesting a general interdependency of active enhancers and expression of long ncRNAs. This dependency is not identified using previous enhancer prediction algorithms that do not account for expression of their downstream targets. The predicted enhancers that overlap annotated long ncRNAs generally have a lower ratio of H3K4me1 to H3K4me3, suggesting that enhancers expressing long ncRNAs might be associated with specific epigenetic marks. In conclusion, we demonstrate the tissue-specific predictive power of PreSTIGE and provide evidence for thousands of long ncRNAs that are expressed from active tissue-specific enhancers, suggesting a particularly important functional relationship between long ncRNAs and enhancer activity in determining tissue-specific gene expression.     

Long ncRNA expression associates with tissue-specific enhancers

Long non-coding RNAs (ncRNA) have recently been demonstrated to be expressed from a subset of enhancers and to be required for the distant regulation of gene expression. Several approaches to predict enhancers have been developed based on various chromatin marks and occupancy of enhancer-binding proteins. Despite the rapid advances in the field, no consensus how to define tissue specific enhancers yet exists. Here, we identify 2,695 long ncRNAs annotated by ENCODE (corresponding to 28% of all ENCODE annotated long ncRNAs) that overlap tissue-specific enhancers. We use a recently developed algorithm to predict tissue-specific enhancers, PreSTIGE, that is based on the H3K4me1 mark and tissue specific expression of mRNAs. The expression of the long ncRNAs overlapping enhancers is significantly higher when the enhancer is predicted as active in a specific cell line, suggesting a general interdependency of active enhancers and expression of long ncRNAs. This dependency is not identified using previous enhancer prediction algorithms that do not account for expression of their downstream targets. The predicted enhancers that overlap annotated long ncRNAs generally have a lower ratio of H3K4me1 to H3K4me3, suggesting that enhancers expressing long ncRNAs might be associated with specific epigenetic marks. In conclusion, we demonstrate the tissue-specific predictive power of PreSTIGE and provide evidence for thousands of long ncRNAs that are expressed from active tissue-specific enhancers, suggesting a particularly important functional relationship between long ncRNAs and enhancer activity in determining tissue-specific gene expression.