Ferroptosis in Cancer Progression: Role of Noncoding RNAs

Ferroptosis is a novel form of programmed cell death, and it is characterized by iron-dependent oxidative damage, lipid peroxidation and reactive oxygen species accumulation. Notable studies have revealed that ferroptosis plays vital roles in tumor occurrence and that abundant ferroptosis in cells can inhibit tumor progression. Recently, some noncoding RNAs (ncRNAs), particularly microRNAs, long noncoding RNAs, and circular RNAs, have been shown to be involved in biological processes of ferroptosis, thus affecting cancer growth. However, the definite regulatory mechanism of this phenomenon is still unclear. To clarify this issue, increasing studies have focused on the regulatory roles of ncRNAs in the initiation and development of ferroptosis and the role of ferroptosis in progression of various cancers, such as lung, liver, and breast cancers. In this review, we systematically summarized the relationship between ferroptosis-associated ncRNAs and cancer progression. Moreover, additional evidence is needed to identify the role of ferroptosis-related ncRNAs in cancer progression. This review will help us to understand the roles of ncRNAs in ferroptosis and cancer progression and may provide new ideas for exploring novel diagnostic and therapeutic biomarkers for cancer in the future.     

Noncoding RNAs in alcoholic liver disease

Alcoholic liver disease (ALD) is a complex process with high morbitity and can cause liver dysfunction, which contains a wide spectrum of hepatic lesions, including steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. To date, the molecular mechanisms for ALD have not been fully explored and an effective therapy is still missing. Overwhelming evidence shows dysregulation of noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), is correlated with etiopathogenesis and progress of ALD including hepatocyte damage, disrupted lipid metabolism, aggressive inflammatory responses, oxidative stress, programmed cell death, fibrosis, and epigenetic changes induced by alcohol. For example, circulating miRNA-122 is a marker of hepatocyte damage, and miRNA-155 is a potential marker of inflammation, indicating their diagnosis therapeutic potential in ALD. In addition, roles for long noncoding RNAs (lncRNAs) and circular RNAs in ALD are being uncovered. Further, circulating ncRNAs and exosome-derived ncRNAs have attracted more attention lately, suggesting a role in the prevention and treatment of ALD. This review covers the roles of ncRNAs in ALD, and the potential uses as markers for diagnosis and therapeutic options.     

Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer

Breast cancer (BC) is the most frequently occurring malignancy in women worldwide. Despite the substantial advancement in understanding the molecular mechanisms and management of BC, it remains the leading cause of cancer death in women. One of the main reasons for this obstacle is that we have not been able to find the Achilles heel for the BC as a highly heterogeneous disease. Accumulating evidence has revealed that noncoding RNAs (ncRNAs), play key roles in the development of BC; however, the involving of complex regulatory interactions between the different varieties of ncRNAs in the development of this cancer has been poorly understood. In the recent years, the newly discovered mechanism in the RNA world is “competing endogenous RNA (ceRNA)” which proposes regulatory dialogues between different RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). In the latest BC research, various studies have revealed that dysregulation of several ceRNA networks (ceRNETs) between these ncRNAs has fundamental roles in establishing the hallmarks of BC development. And it is thought that such a discovery could open a new window for a better understanding of the hidden aspects of breast tumors. Besides, it probably can provide new biomarkers and potential efficient therapeutic targets for BC. This review will discuss the existing body of knowledge regarding the key functions of ceRNETs and then highlights the emerging roles of some recently discovered ceRNETs in several hallmarks of BC. Moreover, we propose for the first time the “ceRnome” as a new term in the present article for RNA research.     

Emerging regulatory mechanisms of noncoding RNAs in topologically associating domains

Topologically associating domains (TADs) are integral to spatial genome organization, instructing gene expression, and cell fate. Recently, several advances have uncovered roles for noncoding RNAs (ncRNAs) in the regulation of the form and function of mammalian TADs. Phase separation has also emerged as a potential arbiter of ncRNAs in the regulation of TADs. In this review we discuss the implications of these novel findings in relation to how ncRNAs might structurally and functionally regulate TADs from two perspectives: moderating loop extrusion through interactions with architectural proteins, and facilitating TAD phase separation. Additionally, we propose future studies and directions to investigate these phenomena.     

The coded functions of noncoding RNAs for gene regulation

For eukaryotes, fine tuning of gene expression is necessary to coordinate complex genetic information. Recent studies have shown that noncoding RNAs (ncRNAs) play central roles in this process. For example, ncRNAs participate in multiple diverse functions such as mRNA degradation, epigenetic regulation and alternative splicing. The findings regarding this new player in gene regulation suggest that the mechanism of gene regulation is much more complicated and subtle than previously thought. In this review, new findings concerning the role of ncRNAs in gene regulation are discussed.     

New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases

Neurodegenerative diseases (NDs) are a diversity of neurological disorders characterized by the progressive degeneration of the structure and function of the central nervous system (CNS). The most common NDs are Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Recently, many studies have investigated associations between common NDs with noncoding RNAs (ncRNAs) molecules. ncRNAs are regulatory molecules in the normal functioning of the CNS. Two of the most important ncRNAs are microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). These types of ncRNAs are involved in different biological processes including brain development, maturation, differentiation, neuronal cell specification, neurogenesis, and neurotransmission. Increasing data has demonstrated that miRNAs and lncRNAs have strong correlations with the development of NDs, particularly gene expression. Besides, ncRNAs can be introduced as new biomarkers for diagnosis and prognosis of NDs. Hence, in this review, we summarized the involvement of various miRNAs and lncRNAs in most common NDs followed by a correlation of ncRNAs dysregulation with the AD, PD, and HD.     

非编码长链RNA与基因表达调控

近年来,在小鼠全长cDNA文库大规模测序中发现一类新的转录物——非编码长链RNA(long noncoding RNA,lncRNA),引起了科学界的关注.lncRNA长度大于200个核苷酸,无蛋白质编码功能,在真核细胞基因组中被普遍转录.lncRNA种类繁多,数量庞大,占哺乳动物基因组转录物的绝大部分.相对于研究较多的非编码小RNA,lncRNA的功能目前尚不完全清楚.但越来越多的研究发现,lncRNA在多个水平调控基因的表达,在胚胎发育、物种进化、细胞分化和某些疾病如神经退行性疾病及肿瘤的发生过程中起着重要作用.本文在简要介绍lncRNA基本概念的基础上,结合当前研究成果,就lncRNA在转录水平、转录后水平和表观遗传水平调控基因表达的机制作一综述.     

Noncoding RNAs in acute kidney injury

Acute kidney injury (AKI), caused by various stimuli including ischemia reperfusion, nephrotoxic insult, and sepsis, is characterized by abrupt decline of kidney function. Till now, the molecular mechanisms for AKI have not been fully explored and the effective therapies are still lacking. Noncoding RNAs (ncRNAs), a group of biomolecules function at RNA level, are involved in a wide range of physiopathological processes including AKI. MicroRNAs (miRNAs) are the most extensively studied ncRNAs in AKI. Evidence indicated that miRNAs are altered significantly in various types of AKI. Gain-and-loss-of-function studies demonstrated that miRNAs, such as miR-24, miR-126, miR-494, and miR-687, may bind to the 3′-untranslated region of their target genes to regulate inflammation, programmed cell death, and cell cycle in the injury and repair stages of AKI, indicating their therapeutic potential in AKI. In contrast, functions of long noncoding RNAs and circular RNAs in AKI are hot topics but still largely unknown. Additionally, ncRNAs packaged in exosome can be detected in circulation and urine, they may serve as specific biomarkers for AKI. This review summarized the alteration and functional role of ncRNAs and their therapeutic potential in AKI.     

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.     

长非编码RNA的作用机制及在肿瘤发生发展中的意义

功能基因组学的飞速发展将越来越多的目光引向了对非编码转录产物功能的研究。在人的转录组中,存在着一类长度大于200nt,但并不具备编码蛋白质功能的基因转录产物,即长非编码RNA(long noncoding RNA,lncRNA)。相比于小分子RNA,它们仍是目前基因组转录产物中较为陌生的部分。在整个基因组转录产物中,lncRNA所占的比例远远超过编码RNA所占的比例。不同于编码RNA,lncRNA的保守性要差得多,然而在其分子内部,却含有较为保守的局部区段,且其表达具有时空特异性,这些现象都提示了lncRNA具有重要的生理生化功能。越来越多的研究表明,lncRNA在基因表达调控方面发挥着十分重要的作用,与物种进化、胚胎发育、物质代谢以及肿瘤发生等都有着紧密的联系,其功能的深入研究将使目前对细胞的结构网络和调控网络的认识带来革命性的变化,具有不可估量的科学和临床价值。该文将着重讨论lncRNA在不同层面上对基因表达的调控机制以及在肿瘤发生发展中的意义。     

非编码RNA与病毒性心肌炎

病毒性心肌炎(Viral myocarditis,VMC)是一种由病毒感染所引起的以心肌细胞炎症为特征的疾病。由于病毒性心肌炎的发病机制尚未完全研究清楚,因此该病的诊断及治疗对于临床医生来说仍具有极大的挑战性。非编码RNAs (Non-coding RNAs,ncRNAs)是一类不具有编码蛋白质功能的RNA,越来越多的研究表明ncRNAs参与到调控VMC的发生和发展过程中,这可能成为VMC的治疗或诊断的新研究靶点。文中对近3年来关于ncRNAs在VMC的发病机制及诊断中可能发挥的作用进行了综述。     

长非编码RNA研究进展

长非编码RNA是指一类长度大于200个核苷酸、不编码蛋白质的非编码RNA.越来越多的研究表明,人类基因组中高达90%的非编码蛋白质的区段同样具有重要作用,而不是所谓的"转录噪声".针对长非编码RNA的功能研究表明,其在转录起始的调控、转录及转录后的调控中均发挥着重要作用,因而影响着各种各样的生物学过程.本综述围绕近几年长非编码RNA的研究成果,总结了长非编码RNA的起源与进化、新型的长非编码RNA类型、典型的长非编码RNA作用机制以及长非编码RNA在发育与细胞重编程过程中的研究,同时也概述了长非编码RNA与表观遗传调控和癌症的关系以及长非编码RNA研究的相关技术.系统发现长非编码RNA并阐明其功能机制,将对现代生命科学具有重大的意义.     

Application of exosome-derived noncoding RNAs in bone regeneration: Opportunities and challenges

With advances in the fields of regenerative medicine, cell-free therapy has received increased attention. Exosomes have a variety of endogenous properties that provide stability for molecular transport across biological barriers to cells, as a form of cell-to-cell communication that regulates function and phenotype. In addition, exosomes are an important component of paracrine signaling in stem-cell-based therapy and can be used as a stand-alone therapy or as a drug delivery system. The remarkable potential of exosomes has paved the pathway for cell-free treatment in bone regeneration. Exosomes are enriched in distinct noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs and circular RNAs. Different ncRNAs have multiple functions. Altered expression of ncRNA in exosomes is associated with the regenerative potential and development of various diseases, such as femoral head osteonecrosis, myocardial infarction, and cancer. Although there is increasing evidence that exosome-derived ncRNAs (exo-ncRNAs) have the potential for bone regeneration, the detailed mechanisms are not fully understood. Here, we review the biogenesis of exo-ncRNA and the effects of ncRNAs on angiogenesis and osteoblast- and osteoclast-related pathways in different diseases. However, there are still many unsolved problems and challenges in the clinical application of ncRNA; for instance, production, storage, targeted delivery and therapeutic potency assessment. Advancements in exo-ncRNA methods and design will promote the development of therapeutics, revolutionizing the present landscape.     

长链非编码RNA生物学功能及其意义研究进展

人类基因组DNA核苷酸序列中约93%能被转录为RNA,其中仅2%的转录产物被翻译为蛋白质,余下98%属于非编码RNA（non-coding RNA,ncRNA）。ncRNA中长度超过200 nt的称为长链非编码RNA（long non-coding RNA,LncRNA）,长期以来LncRNA被认为是转录过程中的副产物而不具有生物学功能。近年随着微小RNA（microRNA,miRNA）的研究进展,揭示了ncRNA在人类基因转录后调节、细胞生长、分化、增殖中起着相当重要的作用。同时也提示,相比miRNA,在细胞内转录比例更高的LncRNA具有极其复杂而重要的生物学功能,并与人类疾病密切相关。结合LncRNA的表观遗传学功能及其病理生理意义作一简述。     

Roles of noncoding RNAs in drug resistance in multiple myeloma

Despite the administration of new effective drugs in recent years, relapse and drug resistance are still the main obstacles in multiple myeloma (MM) treatment, making MM an incurable disease. To overcome drug resistance in MM, it is critical to understand the underlying mechanisms of malfunctioning gene expression and develop novel targeted therapies. During the past few decades, with the discovery and characterization of noncoding RNAs (ncRNAs), the landscape of dysregulated ncRNAs of cancers as well as their biological and pathobiological functions in tumorigenesis and drug resistance have been recognized. Studies about ncRNAs improved the understanding of variations of drug response among individuals at a level distinguished from genetic polymorphism, and provided with new orientations for targeted therapies. In this review, we will summarize the emerging impact and underlying molecular mechanisms of the most relevant classes of ncRNAs in drug resistance of MM, and discuss the potential as well as strategies of treating ncRNAs as therapeutic targets.     

RNA结合蛋白与非编码RNA调节关系的研究进展

近年来,越来越多的研究表明,RNA结合蛋白(RNA binding protein,RBP)与多种类型的非编码RNAs(noncoding RNA,ncRNAs)具有互相调节的关系,且调节机制形式多样。一方面,RBP可以调节ncRNA的生物合成、稳定性和功能;另一方面,ncRNA也可以影响RBP的功能和结构。同时,RBP和ncRNA的相互作用还在其他靶基因的调节上起着重要的作用,从而参与众多的生物过程,如组织发育、代谢性疾病、神经退行性疾病、抗病毒免疫和各种癌症等。该文就RBP与常见类型的ncRNAs,包括miRNA、lncRNA、circRNA的相互作用方式和调节机制的研究进展作一综述。     

Molecular functions of small regulatory noncoding RNA

Recently, using large-scale genomic sequencing, a great number of small noncoding RNAs (ncRNA) has been discovered. Short ncRNAs can be classified into three major classes — small interfering RNA (siRNA), microRNA (miRNA), and piwi-interacting RNA (piRNA). These short ncRNAs ranging from 20 to 300 nt in size are now recognized as a new paradigm of gene regulation for controlling many biological processes. In this paper, we review the biogenesis and recent research on the functions of small regulatory non-coding RNAs and aim at understanding their important functions in living organisms.