RNA异常与肿瘤调控研究进展

肿瘤的发生是一个多因素、多步骤的过程,其根本原因是细胞稳态的失衡.近年研究发现,在肿瘤的发生、发展中除了蛋白质功能紊乱、DNA突变之外,还存在着大量RNA的异常,包括异常的microRNA(miRNA)、长链非编码RNA(long non-coding RNA,IncRNA)、循环RNA等;此外,肿瘤细胞中还存在RNA转录、加工及调控功能的异常,如RNA选择性剪接、RNA编辑、竞争性内源RNA调控等.这些非编码RNA可以在转录后水平及表观遗传学水平调控癌基因和抑癌基因的功能,影响肿瘤的发生和发展,是肿瘤诊断、治疗及预后判断的潜在靶标.竞争性内源RNA使得lncRNA与mRNA通过miRNA相互调控,以“miRNA结合位点”为媒介,形成RNA调控网络.RNA选择性剪接使得癌基因或抑癌基因产生功能异常的转录本,进而影响其生物学功能.肿瘤中究竟哪些机制导致这些RNA表达及功能的异常,RNA表达及功能的异常又如何影响肿瘤的发生和发展,有哪些表达或功能异常的RNA可以作为肿瘤诊断及预后判断的标志物,又有哪些RNA可以作为肿瘤靶向治疗的靶标?等等问题亟待深入探讨,RNA异常与肿瘤调控已成为肿瘤研究的前沿热点领域.     

MicroRNAs与癌症

MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that are involved in oncogenesis and show remarkable tissue specificity. miRNAs are approximately 22 nt non-coding RNAs, which regulate gene expression in a sequence-specific manner via translational inhibition or messenger RNA (mRNA) degradation, thus affecting various cellular processes. Since the discovery of their fundamental mechanisms of action, the field of miRNAs has opened a new era in the understanding of small noncoding RNAs. Recent evidence has shown that miRNA controls cell growth, apoptosis, and differentiation. Cancer is a complex genetic disease caused by abnormalities in gene structure and expression, moreover, miRNA expression correlates with cancers and could have a crucial function in tumor progression. Bioinformatic data indicate that each miRNA can control hundreds of target genes, but identification of the accurate miRNA targets will be crucial to exploit the emerging knowledge of miRNA contribution to cancer process.     

Discovery of the hidden coding information in cancers: Mechanisms and biological functions

Most proteins are derived from the translation of coding sequence (CDS) in messenger RNAs (mRNAs). However, accumulating evidence has revealed an unexpected abundance of translation in putative non-coding genomes, especially 5′ untranslated region (5′ UTR) of mRNAs or non-coding RNA species (ncRNA) such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Notably, many of these UTR- or ncRNA-encoded micropeptides/proteins play important roles in human malignancies. In this review, we describe recent advances in our understanding of the mechanisms underlying the translation of non-coding regions or ncRNAs and the methods to discover the hidden coding information. Furthermore, we summarize the biological functions of UTR- or ncRNA-encoded micropeptides/proteins in cancers and discuss their potential as clinical biomarkers for cancer diagnosis and as therapeutic targets for cancer treatment.     

ceRNA在肿瘤中的研究进展

竞争性内源RNA(competing endogenous RNA,ceRNA)是一类能与miRNA结合位点（miRNA response element,MRE）结合从而抑制miRISC形成,并能进一步增加相应mRNA的表达来达到RNA间相互沟通及转录后调控基因表达的一类非编码RNA。ceRNA主要包括长链非编码RNA（long non-coding RNA,lncRNA）、环状RNA（circular RNA,circRNA）、假基因、人工合成miRNA抑制剂及病毒miRNA抑制剂等。目前越来越多的研究表明ceRNA在肿瘤的基因调控及肿瘤细胞增殖、凋亡、细胞周期、侵袭和转移等各种生物过程中发挥重要作用。本文从ceRNA分类、调控网络及ceRNA在不同肿瘤中的研究进展作一综述。     

MicroRNA in pancreatic cancer: Pathological,diagnostic and therapeutic implications

MicroRNAs (miRNAs) are a group of small non-coding RNA molecules of 17–25 nucleotides (nt) in length, predicted to control the activity of about 30% of all protein-coding genes in mammals. Altered expressions of miRNAs are reported in various cancers and may associate with cancer pathogenesis, apoptosis, and cell growth, thereby functioning as either tumor suppressors or oncogenes. Recent reports showed that deregulation of miRNA contribute to tumor development and progression and hence, have diagnostic and prognostic value in several human malignancies. This review discusses the current status of miRNA in pancreatic cancer development, progression, diagnosis, and therapy.     

人类癌症中长链非编码RNA与miRNA相互作用的研究进展

人类基因组中大部分为非编码区,转录产生非编码RNA（ncRNA）。这些ncRNA可以在表观遗传学水平及转录后水平调控癌基因和抑癌基因的表达,影响肿瘤的发生和发展,是肿瘤诊断、治疗及预后判断的潜在靶标。微小RNA（miRNA） 和长链非编码RNA（lncRNA） 是ncRNA的两个重要分类。其中,lncRNA通过多种机制在不同水平进行基因表达调控,发挥其生物学功能,这些机制包括基因印迹、染色质重塑、细胞周期调控、选择性剪接、mRNA降解和翻译调控等。近年来,miRNA和lncRNA在癌症发生发展中相互作用的分子机制引起了人们的注意。本文主要就这两者在癌症发生发展过程中的相互作用机制及研究方法进行综述。     

A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes

The known classes of genes that function as tumor suppressors and oncogenes have recently been expanded to include the microRNA (miRNA) family of regulatory molecules. miRNAs negatively regulate the stability and translation of target messenger RNAs (mRNA) and have been implicated in diverse processes such as cellular differentiation, cell-cycle control and apoptosis. Examination of tumor-specific miRNA expression profiles has revealed widespread dysregulation of these molecules in diverse cancers. Although studies addressing their role in cancer pathogenesis are at an early stage, it is apparent that loss- or gain-of-function of specific miRNAs contributes to cellular transformation and tumorigenesis. The available evidence clearly demonstrates that these molecules are intertwined with cellular pathways regulated by classical oncogenes and tumor suppressors such as MYC, RAS and p53. Incorporation of miRNA regulation into current models of molecular cancer pathogenesis will be essential to achieve a complete understanding of this group of diseases.     

长链非编码RNA在非小细胞肺癌中的研究进展

肺癌是全球发病率最高,也是死亡率最高的恶性肿瘤之一,非小细胞肺癌占肺癌的绝大部分。目前发现大量的非编码RNA(long non-coding RNA,lncRNAs)极大地改变了人们对肿瘤的理解。lncRNAs是一组非编码的RNA(ncRNAs)超过200个核苷酸,不具有蛋白质编码能力。越来越多的证据表明,特定的lncRNAs可能参与肿瘤发生的过程。它们参与了多重分子调控以及基因表达变化相关的途径,重要的是据报道,lncRNAs与肺癌的治疗有关,包括化疗、分子靶向治疗等,它们可以作为潜在肺癌的诊断生物学指标或目标。本文将对长链非编码RNA在非小细胞肺癌中的研究进展作一综述。     

miRNA与宫颈癌发病机制的研究进展

微小核糖核酸(microRNA,miRNA）是在调节基因表达过程中发挥作用的一类非编码的内源RNA。宫颈癌是常见的妇科恶性肿瘤。随着科研水平的提高,人们对miRNA研究的深入,大量的研究证实miRNA与宫颈癌的发病机制相关,本文就近年来与宫颈癌发病机制相关的miRNA作一综述。     

miRNA在原发性肝癌中的研究进展

原发性肝癌是世界范围内最常见和最具侵袭性的恶性肿瘤之一。miRNA是一系列调控基因转录后表达的非编码小RNA。研究发现,miRNA具有癌基因和抑癌基因的作用,在肿瘤的发生和发展中起着重要的作用。已有证据表明,原发性肝癌中存在一些异常表达的miRNA,它们多靶向于肝癌发生、发展相关的基因和信号通路,从而广泛调节肝癌细胞的增殖、分化、凋亡、侵袭和转移等重要的涉及癌细胞发生演变的病理过程。异常表达的miRNA及其功能靶标的发现不仅丰富了肝癌的发病机制,也为探索新的基因靶向治疗提供了可能; miRNA表达谱还与肝癌病理类型、恶性程度、分期、分级等临床病理过程密切相关,提示miRNA不仅可能用于肝癌诊断及个体化治疗,也可能作为判断预后的工具。本文就肝癌发生、发展、诊断、靶向治疗和预后中发挥重要作用的miRNA及其作用靶点作一综述。     

microRNA-613在恶性肿瘤中的研究进展

微小RNA（microRNA,miRNA）作为一种在恶性肿瘤发生中起到非常重要作用的短链非编码RNA,通过与其靶基因的特异性结合从转录后水平调控肿瘤相关基因的表达。微小RNA-613（microRNA-613,miR-613）定位在人染色体12p13.1,通过对靶基因的调控,参与肿瘤细胞的增殖、分化、凋亡、癌周浸润等恶性进程的调控。近年来研究表明,miR-613在多种肿瘤中异常表达并与肿瘤的临床特征及预后密切相关。鉴于其在恶性肿瘤中的重要作用,miR-613或可成为分子靶向治疗的新靶点。     

非编码RNA在膀胱癌中的研究进展

膀胱癌是全世界最常见的癌症之一,虽然手术结合化疗和放疗在一定程度上改善了患者的预后,但大多数肌肉浸润性膀胱癌患者的预后仍然很差。而且,膀胱癌的确切机制和关键调节因子尚不清楚。最近的研究表明,一些非编码RNA在膀胱癌中表达失调,对膀胱癌的发生发展起着至关重要的作用。更重要的是,非编码RNA可作为膀胱癌的诊断和预后的生物标志物。本综述旨在总结近期的研究进展,这些研究表明了包括miRNA、lncRNA、circRNA在内的三类非编码RNA在膀胱癌中的调控机制,以及它们作为临床诊断或预后生物标志物的潜在作用。     

miRNA相关SNPs与肺癌遗传易感性关系的研究进展

肺癌是世界最常见的癌症,已成为癌症死亡的主要原因。microRNAs（miRNAs）是一类高度保守、内源性非蛋白编码、长度约21~24核苷酸的小分子单链RNA,在基因调控中扮演着重要的角色。miRNA相关单核苷酸多态性（miRNA-related single nucleotide polymorphisms或miR-SNPs）主要包括miRNA基因SNPs、生物合成通路相关基因SNPs和miRNA靶基因中的SNPs,可通过影响miRNA的成熟过程、表达水平及与靶mRNA的识别结合等,使miRNA调控网络发生异常,从而参与肿瘤的发生发展。本文对miRNA相关SNPs与肺癌遗传易感性关系的研究进展进行综述,旨在为肺癌等恶性肿瘤的预防和控制提供参考。     

Non-coding RNAs (miRNAs and lncRNAs) and their roles in lymphogenesis in all types of lymphomas and lymphoid malignancies

Contemporary developments in molecular biology have been combined with discoveries on the analysis of the role of all non-coding RNAs (ncRNAs) in human diseases, particularly in cancer, by examining their roles in cells. Currently, included among these common types of cancer, are all the lymphomas and lymphoid malignancies, which represent a diverse group of neoplasms and malignant disorders. Initial data suggest that non-coding RNAs, particularly long ncRNAs (lncRNAs), play key roles in oncogenesis and that lncRNA-mediated biology is an important key pathway to cancer progression. Other non-coding RNAs, termed microRNAs (miRNAs or miRs), are very promising cancer molecular biomarkers. They can be detected in tissues, cell lines, biopsy material and all biological fluids, such as blood. With the number of well-characterized cancer-related lncRNAs and miRNAs increasing, the study of the roles of non-coding RNAs in cancer is bringing forth new hypotheses of the biology of cancerous cells. For the first time, to the best of our knowledge, the present review provides an up-to-date summary of the recent literature referring to all diagnosed ncRNAs that mediate the pathogenesis of all types of lymphomas and lymphoid malignancies.