Searching genomes for noncoding RNA using FastR

The discovery of novel noncoding RNAs has been among the most exciting recent developments in biology. It has been hypothesized that there is, in fact, an abundance of functional noncoding RNAs (ncRNAs) with various catalytic and regulatory functions. However, the inherent signal for ncRNA is weaker than the signal for protein coding genes, making these harder to identify. We consider the following problem: Given an RNA sequence with a known secondary structure, efficiently detect all structural homologs in a genomic database by computing the sequence and structure similarity to the query. Our approach, based on structural filters that eliminate a large portion of the database while retaining the true homologs, allows us to search a typical bacterial genome in minutes on a standard PC. The results are two orders of magnitude better than the currently available software for the problem. We applied FastR to the discovery of novel riboswitches, which are a class of RNA domains found in the untranslated regions. They are of interest because they regulate metabolite synthesis by directly binding metabolites. We searched all available eubacterial and archaeal genomes for riboswitches from purine, lysine, thiamin, and riboflavin subfamilies. Our results point to a number of novel candidates for each of these subfamilies and include genomes that were not known to contain riboswitches.     

Taurine-upregulated gene 1: A functional long noncoding RNA in tumorigenesis

Taurine-upregulated gene 1 (TUG1) is a 7.1 kb long noncoding RNA (lncRNA) first recognized in 2005 as an important element for retinal development in rodents. Subsequently, this lncRNA has been shown to participate in oncogenic processes through alteration in chromatin structure, sponging microRNAs, and affecting the expression of some cancer-related pathways. While most of the studies have revealed an oncogenic role for this lncRNA, some reports have shown downregulation of TUG1 in lung cancer samples compared with noncancerous samples. In triple negative breast cancer samples, the expression of this lncRNA has been decreased. Besides, its expression has been higher in HER2-enriched and basal-like subtypes compared with luminal A. In the current review, we discuss the latest literature about the expression pattern and functional roles of TUG1 in diverse cancer types. In addition, its role in epithelial−mesenchymal transition and activation of Wnt/β-catenin pathway in human malignancies will be explored.     

The long noncoding RNA CIRBIL is a regulator of steroidogenesis in mice

Infertility affects roughly 8–12 % of couples worldwide, and in above 50 % of couples, male factors are the primary or contributing cause. Many long noncoding RNAs (lncRNAs) are detected in the testis, but their functions are not well understood. CIRBIL was 862 nucleotides in length and was found to be localized mostly in the cytosol of Leydig cell, a small portion was positioned inside the seminiferous tubules. Loss of CIRBIL in mice resulted in male subfertility, characterized by smaller testis and increased germ cell apoptosis. Deletion of CIRBIL significant decreased the number of sperm and impaired the integrity of sperm head and tail. In CIRBIL KO mice, testosterone levels in serum and expression of testosterone biosynthesis genes (STAR and 3β-HSD) were both reduced. Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were primarily enriched in steroid synthesis process in CIRBIL-binding proteins. Protein-protein (PPI) interaction networks revealed that both cis- and trans-regulated target genes of CIRBIL were associated with testosterone synthesis. Collectively, our results strongly suggest that CIRBIL is a regulator of steroid hormone synthesis.     

A prognostic 11 long noncoding RNA expression signature for breast invasive carcinoma

Breast cancer, the most common cancer in women worldwide, is associated with high mortality. The long non-coding RNAs (lncRNAs) with a little capacity of coding proteins is playing an increasingly important role in the cancer paradigm. Accumulating evidences demonstrate that lncRNAs have crucial connections with breast cancer prognosis while the studies of lncRNAs in breast cancer are still in its primary stage. In this study, we collected 1052 clinical patient samples, a comparatively large sample size, including 13 159 lncRNA expression profiles of breast invasive carcinoma (BRCA) from The Cancer Genome Atlas database to identify prognosis-related lncRNAs. We randomly separated all of these clinical patient samples into training and testing sets. In the training set, we performed univariable Cox regression analysis for primary screening and played the model for Robust likelihood-based survival for 1000 times. Then 11 lncRNAs with a frequency more than 600 were selected for prediction of the prognosis of BRCA. Using the analysis of multivariate Cox regression, we established a signature risk-score formula for 11 lncRNA to identify the relationship between lncRNA signatures and overall survival. The 11 lncRNA signature was validated both in the testing and the complete set and could effectively classify the high-/low-risk group with different OS. We also verified our results in different stages. Moreover, we analyzed the connection between the 11 lncRNAs and the genes of ESR1, PGR, and Her2, of which protein products (ESR, PGR, and HER2) were used to classify the breast cancer subtypes widely. The results indicated correlations between 11 lncRNAs and the gene of PGR and ESR1. Thus, a prognostic model for 11 lncRNA expression was developed to classify the BRAC clinical patient samples, providing new avenues in understanding the potential therapeutic methods of breast cancer.     

The long noncoding RNA glycoLINC assembles a lower glycolytic metabolon to promote glycolysis

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Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation

The competitive endogenous RNA (ceRNA) hypothesis suggests that a long noncoding RNA (lncRNA) can function as sinks for pools of microRNAs (miRNAs); thereby, in the presence of ceRNA, messenger RNAs (mRNAs) targeted by specific miRNAs can liberate and translate to protein. Maternally expressed gene 3 (MEG3) is a lncRNA, which its expression has been detected in various normal tissues, while it is lost or downregulated in human tumors. The MEG3 is an imprinted gene which, is methylated and suppressed by DNA methyltransferases (DNMTs) family. Also, miRNAs are involved in the regulation of MEG3 gene expression. Interestingly, the lncRNA MEG3 (lnc-MEG3), as a ceRNA affects various cell processes such as proliferation, apoptosis, and angiogenesis by sponging miRNAs. These miRNAs, in turn, regulate different mRNAs in different pathways. This review focuses on the interaction between lnc-MEG3 and experimentally validated miRNAs. In addition, the discussion supplemented by some data obtained from mirPath (v.3) and TarBase (v.8) databanks to provide more details about the pathways affected by this ceRNA.     

长链非编码RNA在白血病发生发展中的调控机制研究进展

长链非编码RNA (Long noncoding RNA,lncRNA) 是一类长度大于200 nt且不具备蛋白编码能力或仅编码微肽的RNA分子。LncRNA参与调控细胞增殖、分化和凋亡等生物学过程,与多种恶性血液病的发生、复发及转移密切相关。文章结合最新研究报道,对lncRNA在白血病发生过程中异常表达的功能、调控机制和潜在临床应用方面进行综述。概括了lncRNA可以通过表观遗传修饰、核糖体RNA转录、竞争性结合miRNA,以及参与糖代谢途径、活化肿瘤相关信号通路等多种方式调控白血病的发生发展及化疗中产生的多药耐药性。这些机制研究为深入了解白血病的发病机理、发现新的预后标志物和潜在的治疗靶标,为解决临床上治疗白血病所面临的患者耐药性的产生和治疗后复发等难题提供了新的参考依据。     

An innovative prognostic model based on autophagy-related long noncoding RNA signature for low-grade glioma

Autophagy is a highly conserved lysosomal degradation process essential in tumorigenesis. However, the involvement of autophagy-related long noncoding RNAs (lncRNAs) in low-grade glioma (LGG) remains unclear. In this study, we established an autophagy-related lncRNA prognostic signature for patients with LGG and assess its underlying functions. We used univariate Cox, least absolute shrinkage and selection operator and multivariate Cox regression models to establish an autophagy-related lncRNA prognostic signature. Kaplan–Meier survival analysis, receiver operating characteristic curve, nomogram, C-index, calibration curve and clinical decision-making curve were used to assess the predictive capability of the identified signature. A signature comprising nine autophagy-related lncRNAs (AL136964.1, ARHGEF26-AS1, PCED1B-AS1, AS104072.1, PRKCQ-AS1, LINC00957, AS125616.1, PSMB8-AS1 and AC087741.1) was identified as a prognostic model. Patients with LGG were divided into the high- and low-risk cohorts based on the median model-based risk score. The survival analysis revealed a 10-year survival rate of 9.3% (95% CI 1.91–45.3%) and 13.48% (95% CI 4.52–40.2%) in high-risk patients in the training and validation sets, respectively, and 48.4% (95% CI 24.7–95.0%) and 48.4% (95% CI 28.04–83.4%) in low-risk patients in the training and validation sets, respectively. This finding suggested a relatively low survival in high-risk patients. In addition, the lncRNA signature was independently prognostic and potentially associated with the progression of LGG. Therefore, the 9-autophagy-related-lncRNA signature may play a crucial role in the diagnosis and treatment of LGG, which may offer new avenues for tumour-targeted therapy.