nc2Cancer:一个研究与癌症相关人类非编码RNA的数据库

伴随着高通量测序技术的飞速发展,许多新型的非编码RNA陆续被发现,比如长链非编码RNA(lncRNA)和环状RNA(Circular RNA)。先前的研究已经表明这些非编码RNA在基因表达调控过程中起着很重要的作用,并且与癌症的发生有着很密切的联系。但是,由于研究者们仍然对它们行使何种功能知之甚少,鉴定这些非编码RNA是否与人类癌症存在密切的相互关系仍然是一个巨大的挑战。为了促进这一领域的研究,这篇文章的作者分析了大规模的RNA相互作用数据,然后建立了数据库nc2Cancer(http://www.bioinfo.tsinghua.edu.cn/nc2Cancer/index.php)。这个数据库的目标便是提供非编码RNA与癌症之间的全面关系。现在,该nc2Cancer数据库包括了三种类型的非编码RNA分子:长链非编码RNA,环状RNA以及由假基因转录而成的RNA。这项研究将有助于研究者更好地去理解非编码RNA的功能以及它们在人类癌症发生过程中所起到的作用。     

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。     

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.     

Understanding the proteome encoded by “non-coding RNAs”:new insights into human genome

A great number of non-coding RNAs(ncRNAs) account for the majority of the genome. The translation of these ncRNAs has been noted but seriously underestimated due to both technological and theoretical limitations. Based on the development of ribosome profiling(Ribo-seq), full length translating RNA analysis(RNC-seq) and mass spectrometry technology, more and more ncRNAs are being found to be translated in different organism, and some of them can produce functional peptides. While recently, not only individual new functional proteins, but also a new proteome have been experimentally discovered to be encoded by endogenous lncRNAs and circRNAs. These new proteins are of biological significance, suggesting the connection of the translation of ncRNAs to human physiology and diseases. Therefore, an in-depth and systematic understanding of the coding capabilities of ncRNAs is necessary for basic biology and medicine. In this review, we summarize the advances in the field of discovering this new proteome, i.e. "ncRNA-coded" proteins.     

Non-coding RNAs regulate tumor cell plasticity

Tumor metastasis is one of the most serious challenges for human cancers as the majority of deaths caused by cancer are associated with metastasis, rather than the primary tumor. Recent studies have demonstrated that tumor cell plasticity plays a critical role in tumor metastasis by giving rise to various cell types which is necessary for tumor to invade adjacent tissues and form distant metastasis. These include differentiation of cancer stem cells (CSCs), or epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET). A growing body of evidence has demonstrated that the biology of tumor cell plasticity is tightly linked to functions of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Therefore, understanding the mechanisms how non-coding RNAs regulate tumor cell plasticity is essential for discovery of new diagnostic markers and therapeutic targets to overcome metastasis.     

Non-coding RNA crosstalk with nuclear receptors in liver disease

The dysregulation of nuclear receptors (NRs) underlies the pathogenesis of a variety of liver disorders. Non-coding RNAs (ncRNAs) are defined as RNA molecules transcribed from DNA but not translated into proteins. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two types of ncRNAs that have been extensively studied for regulating gene expression during diverse cellular processes. NRs as therapeutic targets in liver disease have been exemplified by the successful application of their pharmacological ligands in clinics. MiRNA-based reagents or drugs are emerging as flagship products in clinical trials. Advancing our understanding of the crosstalk between NRs and ncRNAs is critical to the development of diagnostic and therapeutic strategies. This review summarizes recent findings on the reciprocal regulation between NRs and ncRNAs (mainly on miRNAs and lncRNAs) and their implication in liver pathophysiology, which might be informative to the translational medicine of targeting NRs and ncRNAs in liver disease.     

Small noncoding RNAs: Biogenesis,function, and emerging significance in toxicology

In recent years, the discovery of small ncRNAs (noncoding RNAs) has unveiled a slew of powerful riboregulators of gene expression. So far, many different types of small ncRNAs have been described. Of these, miRNAs (microRNAs), siRNAs (small interfering RNAs), and piRNAs (Piwi‐interacting RNAs) have been studied in more detail. A significant fraction of genes in most organisms and tissues is targets of these small ncRNAs. Because these tiny RNAs are turning out to be important regulators of gene and genome expression, their aberrant expression profiles are expected to be associated with cellular dysfunction and disease. In fact, an ever‐increasing number of studies have implicated miRNAs and siRNAs in human health and disease ranging from metabolic disorders to diseases of various organ systems as well as various forms of cancer. Nevertheless, despite the flurry of research on these small ncRNAs, many aspects of their biology still remain to be understood. The following discussion focuses on some aspects of the biogenesis and function of small ncRNAs with major emphasis on miRNAs since these are the most widespread endogenous small ncRNAs that have been called “micromanagers” of gene expression. Their emerging significance in toxicology is also discussed. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:195–216, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20325