Long Non-coding RNAs in the Cytoplasm

An enormous amount of long non-coding RNAs (lncRNAs) transcribed from eukaryotic genome are important regulators in different aspects of cellular events. Cytoplasm is the residence and the site of action for many lncRNAs. The cytoplasmic lncRNAs play indispensable roles with multiple molecular mechanisms in animal and human cells. In this review, we mainly talk about functions and the underlying mechanisms of lncRNAs in the cytoplasm. We highlight relatively well-studied examples of cytoplasmic lncRNAs for their roles in modulating mRNA stability, regulating mRNA translation, serving as competing endogenous RNAs, functioning as precursors of microRNAs, and mediating protein modifications. We also elaborate the perspectives of cytoplasmic lncRNA studies.     

Long non‐coding RNAs in non‐small cell lung cancer as biomarkers and therapeutic targets

Lung cancer‐associated mortality is the most common cause of cancer death worldwide. Non‐coding RNAs (ncRNAs), with no protein‐coding ability, have multiple biological roles. Long non‐coding RNAs (lncRNAs) are a recently characterized class of ncRNAs that are over 200 nucleotides in length. Many lncRNAs have the ability of facilitating or inhibiting the development and progression of tumours, including non‐small cell lung cancer (NSCLC). Because of their fundamental roles in regulating gene expression, along with their involvement in the biological mechanisms underlying tumourigenesis, they are a promising class of tissue‐ and/or blood‐based cancer biomarkers. In this review, we highlight the emerging roles of lncRNAs in NSCLC, and discuss their potential clinical applications as diagnostic and prognostic markers and as therapeutic targets.     

Long non-coding RNAs in hematological malignancies: translating basic techniques into diagnostic and therapeutic strategies

Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization. In this review, we summarize and discuss both conventional and advanced approaches for the identification and functional characterization of lncRNAs related to hematological malignancies. In particular, the utility and advancement of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system as gene-editing tools are envisioned to facilitate the molecular dissection of lncRNAs via different knock-in/out strategies. Besides experimental considerations specific to lncRNAs, the roles of lncRNAs in the pathogenesis and progression of leukemia are also highlighted in the review. We expect that these insights may ultimately lead to clinical applications including development of biomarkers and novel therapeutic approaches targeting lncRNAs.     

Functions and roles of long noncoding RNA in cholangiocarcinoma

Cholangiocarcinoma (CCA) is one of the most fatal cancers in humans, with a gradually increasing incidence worldwide. The efficient diagnostic and therapeutic measures for CCA to reduce mortality are urgently needed. Long noncoding RNAs (lncRNAs) may provide the potential diagnostic and therapeutic option for suppressing the CCA development. LncRNAs are a type of non-protein-coding RNAs, which are larger than 200 nucleotides in length. Increasing evidence reveals that lncRNAs exhibit critical roles in the carcinogenesis and development of CCA. Deregulation of lncRNAs impacts the proliferation, migration, invasion, and antiapoptosis of CCA cells by multiple sophisticated mechanisms. Consequently, lncRNAs likely represent promising biomarkers or intervention targets of CCA. In this review, we summarize current studies regarding the biological functions and regulatory mechanisms of diverse lncRNAs in CCA.     

长非编码RNA与蛋白质的相互作用

长非编码RNA(long non-coding RNA,lncRNA)是一类长度大于200个核苷酸但缺乏蛋白质编码潜力的调控型RNA。lncRNA在真核生物基因组中广泛转录,并且能够在多种层次以灵活的方式对基因表达进行调控。lncRNA能够与染色质修饰复合物及转录因子等蛋白质相互作用,这种相互作用提高了基因表达调控的灵活性和复杂性。本文将介绍部分具有代表性的lncRNA-蛋白质相互作用及其在基因表达调控中的作用。     

Identify the critical protein-coding genes and long noncoding RNAs in cardiac myxoma

Cardiac myxoma (CM) is the most common benign cardiac tumor which is mostly sporadic. Increasing evidence show that protein-coding genes (PCGs) and long noncoding RNAs (lncRNAs) play important roles in the pathology processes of multiple cancers. However, the functional roles and regulatory mechanisms of RNAs interaction in CM are still unclear. In this study, we investigated three pairs of surgically excised CM by high throughput sequencing and screened a set of PCGs and lncRNAs which were differentially expressed and could serve as expression markers in CM. By constructing protein-protein interactions (PPI) and lncRNA-mRNA coexpressing network, we screened out a CM-related hub lncRNA-mRNA modules, which were enriched in different pathways such as MAPK and TGF-beta whose imbalance were validated by q-PCR. In addition, we identified a specific dysregulated competing endogenous RNA (ceRNA) network in CM by integrating lncRNA-miRNA-mRNA interactions. These results will help us to understand the interaction mechanisms of RNAs in CM and provide novel PCGs and lncRNAs as potential therapeutic targets for CM.     

Adaptor proteins in long noncoding RNA biology

Long noncoding RNAs (lncRNAs) are a heterogeneous class of noncoding RNAs that have gained increasing attention due to their vital roles in the regulation of diverse cellular processes. Because lncRNAs are generally expressed at low levels, are poorly conserved, and can act via diverse mechanisms, investigating the molecular mechanisms by which lncRNAs act is challenging. Similar to mRNAs, lncRNAs bind to RNA-binding proteins (RBPs) and in some cases, have been shown to regulate the activity of the RBP they bind to. Furthermore, recent studies have shown that some lncRNAs directly bind to a specific RBP that, in turn, forms a complex with other proteins that mediate the effects of the lncRNA. We termed such RBPs as adaptor proteins because they function as adaptors to recruit other proteins that indirectly associate with the lncRNA. Here, we discuss the emerging roles of adaptor proteins in lncRNA function and propose mechanistic scenarios and strategies to identify adaptor proteins that could play vital roles in the biology of a lncRNA. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen.     

Long non-coding RNAs regulation in adipogenesis and lipid metabolism: Emerging insights in obesity

Obesity is a widespread health problem that brings about various adipose tissue dysfunctions. The balance of energy storage and energy expenditure is critical for normal fat accumulation and lipid metabolism. Therefore, understanding the molecular basis of adipogenesis and thermogenesis is essential to maintain adipose development and lipid homeostasis. Increasing evidence demonstrated that lncRNAs (long non-coding RNAs), a class of non-protein coding RNAs of >200 nucleotides in length, are identified as key regulators in obesity-related biological processes through diverse regulatory mechanisms. In this review, we concentrate on recent and relevant studies on the roles of lncRNAs in regulation of white adipogenesis, brown adipocyte differentiation and lipid metabolism. In addition, the diagnostic and therapeutic potential of lncRNAs is highlighted, and that will make recommendations for the future application of lncRNAs in the treatment of obesity.     

Identification of functional lncRNAs in atrial fibrillation by integrative analysis of the lncRNA-mRNA network based on competing endogenous RNAs hypothesis

A mounting body of evidence has suggested that long noncoding RNAs (lncRNAs) play critical roles in human diseases by acting as competing endogenous RNAs (ceRNAs). However, the functions and ceRNA mechanisms of lncRNAs in atrial fibrillation (AF) remain to date unclear. In this study, we constructed an AF-related lncRNA-mRNA network (AFLMN) based on ceRNA theory, by integrating probe reannotation pipeline and microRNA (miRNA)-target regulatory interactions. Two lncRNAs with central topological properties in the AFLMN were first obtained. By using bidirectional hierarchical clustering, we identified two modules containing four lncRNAs, which were significantly enriched in many known pathways of AF. To elucidate the ceRNA interactions in certain disease or normal condition, the dysregulated lncRNA-mRNA crosstalks in AF were further analyzed, and six hub lncRNAs were obtained from the network. Furthermore, random walk analysis of the AFLMN suggested that lncRNA RP11-296O14.3 may function importantly in the pathological process of AF. All these eight lncRNAs that were identified from previous steps (RP11-363E7.4, GAS5, RP11-410L14.2, HAGLR, RP11-421L21.3, RP11-111K18.2, HOTAIRM1, and RP11-296O14.3) exhibited a strong diagnostic power for AF. The results of our study provide new insights into the functional roles and regulatory mechanisms of lncRNAs in AF, and facilitate the discovery of novel diagnostic biomarkers or therapeutic targets.     

LncRNA-NNT-AS1 contributes to the progression of glioma by miR-582-5p/EZH2 axis

Cytotechnology - Increasing studies have shown that long non-coding RNAs (lncRNAs) had crucial regulatory roles in many diseases. Nevertheless, the biological relevance and mechanisms of the...