A bioinformatics method for predicting long noncoding RNAs associated with vascular disease

Long noncoding RNAs (lncRNAs) play important roles in human diseases including vascular disease. Given the large number of lncRNAs, however, whether the majority of them are associated with vascular disease remains unknown. For this purpose, here we present a genomic location based bioinformatics method to predict the lncRNAs associated with vascular disease. We applied the presented method to globally screen the human lncRNAs potentially involved in vascular disease. As a result, we predicted 3043 putative vascular disease associated lncRNAs. To test the accuracy of the method, we selected 10 lncRNAs predicted to be implicated in proliferation and migration of vascular smooth muscle cells (VSMCs) for further experimental validation. The results confirmed that eight of the 10 lncRNAs (80%) are validated. This result suggests that the presented method has a reliable prediction performance. Finally, the presented bioinformatics method and the predicted vascular disease associated lncRNAs together may provide helps for not only better understanding of the roles of lncRNAs in vascular disease but also the identification of novel molecules for the diagnosis and therapy of vascular disease.     

长链非编码RNA的作用机制及其研究方法

长链非编码RNA(Long non-coding RNA, lncRNA)通过多种机制发挥其生物学功能, 这些机制包括基因印记、染色质重塑、细胞周期调控、剪接调控、mRNA降解和翻译调控等。lncRNA通过这些作用机制在不同水平进行基因表达调控。在研究lncRNA功能的过程中, 研究方法的建立和应用起着非常重要的作用。目前用于lncRNA研究的主要方法有：微阵列、转录组测序、Northern印迹、实时荧光定量逆转录-聚合酶链反应、荧光原位杂交、RNA干扰和RNA结合蛋白免疫沉淀等。文章着重介绍了3种前沿方法, 即：在线快速预测RNA与蛋白质相互作用的catRAPID、RNA纯化的染色质分离(Chromatin isolation by RNA purification, ChIRP)以及非编码RNA沉默与定位分析技术(Combined knockdown and localization analysis of non-coding RNAs, c-KLAN)。     

An atlas and analysis of bovine skeletal muscle long noncoding RNAs

Long noncoding RNAs (lncRNAs) have various biological functions and have been extensively studied in recent years. However, the identification and characterization of bovine lncRNAs in skeletal muscle has been very limited compared with that of lncRNAs in other model organisms. In this study, 7188 bovine skeletal muscle lncRNAs were identified by RNA‐Seq and a stringent screening procedure in four different muscle tissues. These lncRNAs shared many characteristics with other mammalian lncRNAs, such as a shorter open reading frame and lower expression level than for mRNAs. Furthermore, the chromosomal locations and global expression patterns for these lncRNAs are also described in detail. More importantly, we detected the important interaction relationships of lncRNAs–miRNAs–mRNAs related to muscle development among 36 lncRNAs, 62 miRNAs and 12 mRNAs. Our results provide a global expression pattern of lncRNAs specific to bovine skeletal muscle and provide important targets for revealing the function of bovine muscle development by thoroughly studying the interaction relationships of lncRNAs–miRNAs–mRNAs.     

Brain-specific noncoding RNAs are likely to originate in repeats and may play a role in up-regulating genes in cis

The mouse and human brain express a large number of noncoding RNAs (ncRNAs). Some of these are known to participate in neural progenitor cell fate determination, cell differentiation, neuronal and synaptic plasticity and transposable elements derived ncRNAs contribute to somatic variation. Dysregulation of specific long ncRNAs (lncRNAs) has been shown in neuro-developmental and neuro-degenerative diseases thus highlighting the importance of lncRNAs in brain function. Even though it is known that lncRNAs are expressed in cells at low levels in a tissue-specific manner, bioinformatics analyses of brain-specific ncRNAs has not been performed. We analyzed previously published custom microarray ncRNA expression data generated from twelve human tissues to identify tissue-specific ncRNAs. We find that among the 12 tissues studied, brain has the largest number of ncRNAs. Our analyses show that genes in the vicinity of brain-specific ncRNAs are significantly up regulated in the brain. Investigations of repeat representation show that brain-specific ncRNAs are significantly more likely to originate in repeat regions especially DNA/TcMar-Tigger compared with non-tissue-specific ncRNAs. We find SINE/Alus depleted from brain-specific dataset when compared with non-tissue-specific ncRNAs. Our data provide a bioinformatics comparison between brain-specific and non tissue-specific ncRNAs. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.     

Long noncoding RNAs biomarker-based cancer assessment

Cancer diagnosis have mainly relied on the incorporation of molecular biomarkers as part of routine diagnostic tool. The molecular alteration ranges from those involving DNA, RNA, noncoding RNAs (microRNAs and long noncoding RNAs [lncRNAs]) and proteins. lncRNAs are recently discovered noncoding endogenous RNAs that critically regulates the development, invasion, and metastasis of cancer cells. They are dysregulated in different types of malignancies and have the potential to serve as diagnostic markers for cancer. The expression of noncoding RNAs is altered following many diseases, and besides, some of them can be secreted from the cells into the circulation following the apoptotic and necrotic cell death. These secreted noncoding RNAs are known as cell free RNA. These RNAs can be secreted from the cell through the apoptotic body, extracellular vesicles including microvesicle and exosome, and bind to proteins. Since, lncRNAs display high organ and cell specificity, can be found in the blood, urine, tumor tissue, or other tissues or bodily fluids of some patients with cancer, this review summarizes the most significant and up-to-date findings of research on lncRNAs involvement in different cancers, focusing on the potential of cancer-related lncRNAs as biomarkers for diagnosis, prognosis, and therapy.     

Molecular mechanisms of long noncoding RNAs

Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. Here we discuss the emerging archetypes of molecular functions that lncRNAs execute-as signals, decoys, guides, and scaffolds. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution. As new lncRNAs are being discovered at a rapid pace, the molecular mechanisms of lncRNAs are likely to be enriched and diversified.     

长非编码RNA

人类基因组序列的约5%～10%被稳定转录,蛋白质编码基因仅约占1%,其余4%～9%的序列虽能转录,但转录物功能尚不明确。尽管如此,已确证在非蛋白质编码转录物中,含有具备调节功能的非编码RNA(noncoding RNA,ncRNA)。与具有调节功能的短链非编码RNA[如微RNA(microRNA)、小干扰RNA(siRNA),、Piwi-RNA]相比,长非编码RNA(long noncoding RNA,lncRNA)在数量上占大多数。lncRNA通过多种方式产生,以多种途径调节靶基因表达,参与调控生物体生长、发育、衰老、死亡等过程;lncRNA功能异常往往导致疾病发生。本文综述了lncRNA的起源、分类、作用分子机制及lncRNA异常与疾病的相关性等内容,旨在充分了解这一重要新型调控分子。     

Survival analysis for long noncoding RNAs identifies TP53TG1 as an antioncogenic target for the breast cancer

Breast carcinoma is one of the most commonly diagnosed tumors and also one of the deadliest cancers in the female. Long noncoding RNAs (lncRNAs) are emerging as novel targets and biomarkers for breast cancer diagnosis and treatment. In this study, we aimed to study the lncRNAs associated with the outcomes in patients using the breast invasive carcinoma datasets from The Cancer Genome Atlas. The Cox proportional hazards regression model was fitted to each lncRNA. Hierarchy clustering was carried out using these survival-related lncRNAs and the log-rank test was carried out for the clustered groups. DNA methylation status was utilized to identify the lncRNAs regulated by epigenetics. Finally, the coexpressed messenger RNA with the potential lncRNAs were utilized to study the possible functions and mechanisms of lncRNAs. In total, 182 lncRNAs had an impact on the survival time of the patients with a cutoff <0.01. The patients were clustered into three groups using these survival-related genes, which performed significantly different prognosis. Two lncRNAs, which were significantly correlated with the outcomes of breast cancer and were regulated by methylation status, were obtained. These two lncRNAs were TP53TG1 and RP5-1061H20.4. We proposed that TP53TG1 was activated by the wild-type TP53 and performed an impact on the PI3Ks family by binding YBX2 in breast cancer.     

No-nonsense functions for long noncoding RNAs

The mysterious secrets of long noncoding RNAs, often referred to as the Dark Matter of the genome, are gradually coming to light. Several recent papers dig deep to reveal surprisingly complex and diverse functions of these enigmatic molecules.     

Aberrantly expressed long non‐coding RNAs in air pollution‐induced congenital defects

Air pollution has been a serious public health issue over the past few decades particularly in developing countries. Air pollution exposure during pregnancy poses potential threat to offspring as the deleterious substances might pass through placenta to alter foetal development. A growing number of studies have demonstrated that long non‐coding RNAs (lncRNAs) participate in the development of many diseases, including congenital defects. Here, we used RNA sequencing to identify differentially expressed lncRNAs in air pollution‐exposed rat embryos compared with control group. Our data suggested that 554 lncRNAs (216 up‐regulated and 338 down‐regulated) were significantly differentially expressed in the air pollution‐exposed embryos. Moreover, potential cellular functions of these deregulated lncRNAs were predicted via KEGG signal pathway/GO enrichment analyses, which suggested the possible involvements of neurological process, sensory perception of smell and the G‐protein signalling pathway. Furthermore, potential functional network of deregulated lncRNAs and their correlated mRNAs in the development of congenital spinal abnormality was established. Our data suggested that lncRNAs may play a vital role in the pathophysiology of air pollution‐exposed congenital spinal malformation.     

A role of long noncoding RNAs in carcinogenesis

Molecular Biology - The review describes the changes observed in long noncoding RNA (lncRNA) content and function at various stages of carcinogenesis, as well as the prospects of lncRNA application...