动物长链非编码RNA研究进展

长链非编码RNA(long non-coding RNA,lncRNA)是一类广泛存在于动植物体内、长度大于200nt、基本不编码蛋白质的转录本。研究表明,lncRNA能够协助蛋白质复合体转运、参与基因和染色体的激活与失活调控等,在胚胎发育、肌肉生长、脂肪沉积以及免疫应答等过程中发挥重要作用。近年来,在人类基因组计划和ENCODE(The Encyclopedia of DNA Elements)计划推动下,在动物中不仅鉴定出数量众多的lncRNA,而且在lncRNA调控脂肪代谢、肌肉发育以及免疫抗病等重要生物学过程的机理研究方面也取得了突破性的进展。这些研究结果颠覆了lncRNA不编码蛋白的传统观念,提出了lncRNA编码功能性小肽调控生物学过程的新模型。本文主要介绍了动物lncRNA的特征与类型、常用数据库、生物学功能、分子调控模型以及未来lncRNA的研究方向,以期为动物lncRNA功能研究提供参考信息。     

长链非编码RNA研究进展

基因组计划研究表明, 在组成人类基因组的30亿个碱基对中, 仅有1.5%的核酸序列用于蛋白质编码, 其余98.5%的基因组为非蛋白质编码序列。这些序列曾被认为是在进化过程中累积的“垃圾序列”而未予以关注, 但在随后启动的ENCODE研究计划中却发现, 75%的基因组序列能够被转录成RNA, 其中近74%的转录产物为非编码RNA(Non-coding RNA, ncRNA)。在非编码RNA中, 绝大多数转录本的长度大于200个碱基, 这些“长链非编码RNA(Long non-coding RNA, lncRNA)”能够在转录及转录后水平上调节蛋白编码基因的表达, 从而广泛地参与包括细胞分化、个体发育在内的重要生命过程, 其异常表达还与多种人类重大疾病的发生密切相关。文章综述了长链非编码RNA的发现、分类、表达、作用机制以及其在个体发育和人类疾病中的作用。     

Role of long non-coding RNAs in metabolic control

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression by influencing various biological processes including proliferation, apoptosis, differentiation, and senescence. Accumulating evidence implicates lncRNAs in the maintenance of metabolic homeostasis; dysregulation of certain lncRNAs promotes the progression of metabolic disorders such as diabetes, obesity, and cardiovascular diseases. In this review, we discuss our understanding of lncRNAs implicated in metabolic control, focusing on in particular diseases arising from chronic inflammation, insulin resistance, and lipid homeostasis. We have analyzed lncRNAs and their molecular targets involved in the pathogenesis of chronic liver disease, diabetes, and obesity, and have discussed the rising interest in lncRNAs as diagnostic and therapeutic targets improving metabolic homeostasis. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen.     

Conservation analysis of long non-coding RNAs in plants

Long non-coding RNAs (lncRNAs) are gene regulators that have vital roles in development and adaptation to the environment in eukaryotes. However, the structural and evolutionary analyses of plant lncRNAs are limited. In this study, we performed an analysis of lncRNAs in five monocot and five dicot species. Our results showed that plant lncRNA genes were generally shorter and had fewer exons than protein-coding genes. The numbers of lncRNAs were positively correlated with the numbers of protein-coding genes in different plant species, despite a high range of variation. Sequence conservation analysis showed that the majority of lncRNAs had high sequence conservation at the intra-species and sub-species levels, reminiscent of protein-coding genes. At the inter-species level, a subset of lncRNAs were highly diverged at the nucleotide level, but conserved by position. Interestingly, we found that plant lncRNAs have identical splicing signals, and those which can form precursors or targets of miRNAs have a conservative identity in different species. We also revealed that most of the lowly expressed lncRNAs were tissue-specific, while those highly conserved were constitutively transcribed. Meanwhile, we characterized a subset of rice lncRNAs that were co-expressed with their adjacent protein-coding genes, suggesting they may play cis-regulatory roles. These results will contribute to understanding the biological significance and evolution of lncRNAs in plants.     

长链非编码RNA在血液系统肿瘤中作用的研究进展

随着分子生物学技术的飞速发展,人们对于长链非编码RNA(Long non-coding RNA,lncRNA)的研究越来越深入。lncRNA不仅在生物体正常生物活动中不可或缺,还在许多疾病尤其是肿瘤中扮演重要角色。已有的研究表明多种lncRNA与血液系统肿瘤密切相关,具有影响抑癌基因p15表达、p53蛋白功能,以及与miRNA相互作用参与疾病等功能。本文综述了血液系统肿瘤相关的lncRNA并着重介绍与p15、p53、miRNA有关的lncRNA以及它们的相互作用在疾病中发挥的功能,以期能够全面了解血液系统肿瘤相关lncRNA的作用特点,为血液系统肿瘤的研究、诊断以及治疗提供新的思路。     

Natural products: Potential targets of TME related long non-coding RNAs in lung cancer

BackgroundLung cancer is a significant health concern worldwide due to high mortality and morbidity, despite the advances in diagnosis, treatment, and management. Recent experimental evidence from different models suggested long non-coding RNAs (lncRNAs) as major modulators of cancer stem cells (CSCs) in the tumor microenvironment (TME) to support metastasis and drug resistance in lung cancer. Evidence-based studies demonstrated that natural products interfere with TME functions.Purpose of studyTo establish lncRNAs of TME as novel targets of natural compounds for lung cancer management.Study designCurrent study used a combination of TME and lung CSCs, lncRNAs and enrichment and stemness maintenance, natural products and stem cell management, natural products and lncRNAs, natural products and targeted delivery as keywords to retrieve the literature from Scopus, Web of Science, PubMed, and Google Scholar. This study critically reviewed the current literature and presented cancer stem cells' ability in reprogramming lung TME.ResultsThis review found that TME related oncogenic and tumor suppressor lncRNAs and their signaling pathways control the maintenance of stemness in lung TME. This review explored natural phenolic compounds and found that curcumin, genistein, quercetin epigallocatechin gallate and ginsenoside Rh2 are efficient in managing lung CSCs. They modulate lncRNAs and their upstream mediators by targeting signaling and epigenetic pathways. This review also identified relevant nanotechnology-based phytochemical delivery approaches for targeting lung cancer.ConclusionBy critical literature analysis, TME related lncRNAs were identified as potential therapeutic targets, aiming to develop natural product-based therapeutics to treat metastatic and drug-resistant lung cancers.     

Systematic study of human long intergenic non-coding RNAs and their impact on cancer

The functional impact of several long intergenic non-coding RNAs (lincRNAs) has been characterized in previous studies. However, it is difficult to identify lincRNAs on a large-scale and to ascertain their functions or predict their structures in laboratory experiments because of the diversity, lack of knowledge and specificity of expression of lincRNAs. Furthermore, although there are a few well-characterized examples of lincRNAs associated with cancers, these are just the tip of the iceberg owing to the complexity of cancer. Here, by combining RNA-Seq data from several kinds of human cell lines with chromatin-state maps and human expressed sequence tags, we successfully identified more than 3000 human lincRNAs, most of which were new ones. Subsequently, we predicted the functions of 105 lincRNAs based on a coding-non-coding gene co-expression network. Finally, we propose a genetic mediator and key regulator model to unveil the subtle relationships between lincRNAs and lung cancer. Twelve lincRNAs may be principal players in lung tumorigenesis. The present study combines large-scale identification and functional prediction of human lincRNAs, and is a pioneering work in characterizing cancer-associated lincRNAs by bioinformatics.     

The emerging roles of long non-coding RNAs in polyglutamine diseases

Polyglutamine (polyQ) diseases are characterized by trinucleotide repeat amplifications within genes, thus resulting in the formation of polyQ peptides, selective neuronal degeneration and possibly death due to neurodegenerative diseases (NDDs). Long non-coding RNAs (lncRNAs), which exceed 200 nucleotides in length, have been shown to play important roles in several pathological processes of NDDs, including polyQ diseases. Some lncRNAs have been consistently identified to be specific to polyQ diseases, and circulating lncRNAs are among the most promising novel candidates in the search for non-invasive biomarkers for the diagnosis and prognosis of polyQ diseases. In this review, we describe the emerging roles of lncRNAs in polyQ diseases and provide an overview of the general biology of lncRNAs, their implications in pathophysiology and their potential roles as future biomarkers and applications for therapy.