Project description:Recent studies show that long non-coding RNAs (lncRNAs) play crucial roles in human cancers. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of intrahepatic cholangiocarcinoma (ICC) and its progression. In the present study, we performed transcriptomic profiling of five ICC and paired adjacent noncancerous tissues (N) using lncRNA and mRNA microarrays to identify relevant biomarkers in ICC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the microarray results. We sought correlations between the expression levels of lncRNAs and those of target genes. Clinicopathological characteristics and overall survival were compared using the t-test and the Kaplan–Meier method, respectively. A total of 3,054 and 2,111 lncRNAs were significantly up- and down-regulated(fold change?2, p?0.05) in ICC tissues compared to the adjacent NT samples. Bioinformatic analysis indicated that most such genes were related to carcinogenesis, hepatic system disease, and signal transduction. Positive correlations were evident between four pairs of lncRNAs and target mRNAs (RNA43085 and SULF1, RNA47504 and KDM8, RNA58630 and PCSK6, and RNA40057 and CYP2D6). In addition, some lncRNAs and mRNAs were significantly associated with clinicopathological characteristics. The cumulative overall survival rate was significantly associated with low-level expression of CYP2D6 (p=0.005) and PCSK6 (p=0.038). And patients with high expression levels of CYP2D6 and RNA40057 have significant better prognosis (p=0.014). Our results suggested that lncRNA expression profile in ICC tissues is profoundly different from that in NT samples. The lncRNA signature could be used as a biomarker for the prognosis of patients with ICC. Furthermore, the combination of lncRNA and mRNA can reliably predict the survival. The lncRNA expression profiles of cancer and adjacent normal tissues form 5 ICC patients were studied by microarray and an combination of lncRNA and mRNA could be used as a biomarker for the prognosis of patients with ICC

Project description:Background: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from ten healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at one or more than one month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in 2 independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers. We used PolyA+ RNA-seq data from human primary granulocytes of 10 healthy individuals to de novo annotate lncRNAs and mRNAs in this cell type and ribosomal depleted (total) RNA-seq data from seven of these individuals sampled three times to analyze lncRNA amd mRNA expression variability

Project description:Objective: Globally, esophageal cancer is among the most deadly cancer forms. Long non-coding RNAs (lncRNA) are frequently found to have important regulatory roles. We aim to assess the lncRNA expression profile of esophageal squamous cell carcinoma (ESCC) and identify prognosis related lncRNAs. Design: LncRNA expression profiles were studied by microarray in paired tumor and normal tissues from 119 ESCC patients, and validated by qRT-PCR. The 119 patients were subsequently divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random forest supervised classification algorithm and a nearest shrunken centroid algorithm, and validated in test group and further in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by Multivariable Cox regression analysis. Results: LncRNAs showed significantly altered expression in ESCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885•1, XLOC_013014, and ENST00000547963•1) which classified the patients into two groups with significantly different overall survival (median survival 19•2 months vs. not reached, p<0•0001). The signature was applied to the test group (median survival 21•5 months vs. not reached, p=0•0030) and independent cohort (median survival 25•8 months vs. not reached, p=0•0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for ESCC patients. Stratified analysis suggested that the signature was prognostic within clinical stages. Conclusions: Our results suggest that the three-lncRNA signature can serve as a novel biomarker for the prognosis of ESCC patients. Application of it allows for more accurate survival prediction. The lncRNA expression profiles of cancer and adjacent normal tissues form 119 ESCC patients were studied by microarray and an lncRNA signature that can perdict the survival of ESCC patients was identified.

Project description:Recent advances in transcriptome sequencing have enabled the discovery of thousands of long non-coding RNAs (lncRNAs) across many species. Though several lncRNAs have been shown to play important roles in diverse biological processes, the functions and mechanisms of most lncRNAs remain unknown. Two significant obstacles lie between transcriptome sequencing and functional characterization of lncRNAs: identifying truly non-coding genes from de novo reconstructed transcriptomes, and prioritizing the hundreds of resulting putative lncRNAs for downstream experimental interrogation. We present slncky, a computational lncRNA discovery tool that produces a high-quality set of lncRNAs from RNA-sequencing data and further uses evolutionary constraint to prioritize lncRNAs that are likely to be functionally important. Our automated filtering pipeline is comparable to manual curation efforts and more sensitive than previously published computational approaches. Furthermore, we develop a sensitive alignment pipeline for aligning lncRNA loci and propose new evolutionary metrics relevant for analyzing sequence and transcript evolution. Our analysis reveals that evolutionary selection acts in several distinct patterns, and uncovers two notable classes of intergenic lncRNAs: one showing strong purifying selection on RNA sequence and another where constraint is restricted to the regulation but not the sequence of the transcript. To study a comprehensive and comparable set of lncRNAs expressed in the pluripotent state, we analyzed RNA-Seq data from pluripotent cells derived from several strains and species, and grown in two physiological conditions. First we derived ânaÃ¯veâ ES cells (ESCs) from each of three different mice strains: 129SvEv, NOD, and Mus musculus castaneus (cast) mouse, a wild mouse subspecies originally from Thailand, as well as naÃ¯ve induced pluripotent stem (iPS) cells from rat and human. Next, to facilitate comparisons across pluripotent cells from different species, we also cultured mouse and rat cells in âprimedâ epiblast stem cell (EpiSC) culture conditions, since human iPS cells in culture are much more similar molecularly and functionally to mouse primed EpiSCs rather than to a ground state naÃ¯ve ESCs. We polyA selected RNA from each cell type and deeply sequenced on HiSeq2500

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LncReader: identification of dual functional long non-coding RNAs using multi-head self-attention mechanism

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LncReader: identification of dual functional long noncoding RNAs using a multi-head self-attention mechanism.

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