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Transcriptome of hepatocellular carcinoma using CAGE

ABSTRACT: An increasing number of non-coding RNAs (ncRNAs) are implicated in various human diseases including cancer; however ncRNA transcriptome of hepatocellular carcinoma (HCC) remains largely unexplored. We use CAGE (Cap Analysis of Gene Expression) to comprehensively map transcription start sites (TSSs) across different etiologies of human HCC as well as mouse HCC, with particular emphasis on ncRNAs distant from protein-coding genes. We find thousands of significantly up-regulated distal ncRNAs in HCC tumors compared to their matched non-tumors, which are as many as protein-coding genes. Moreover, we identify many LTR retroviral promoters activated in HCC tissues and expressed in a subfamily-specific manner, which account for approximately 20% of the up-regulated distal ncRNAs. The transcripts derived from LTRs, determined by 3' RACE, are multi-exon nuclear ncRNAs typically 0.5-2kb in length. This study sheds light on ncRNA transcriptome of human and mouse HCC.

ORGANISM(S): Mus musculus

PROVIDER: GSE60982 | GEO | 2015/09/10

SECONDARY ACCESSION(S): PRJNA260033

REPOSITORIES: GEO

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Transcriptome of hepatocellular carcinoma using CAGE

Project description:An increasing number of non-coding RNAs (ncRNAs) are implicated in various human diseases including cancer; however ncRNA transcriptome of hepatocellular carcinoma (HCC) remains largely unexplored. We use CAGE (Cap Analysis of Gene Expression) to comprehensively map transcription start sites (TSSs) across different etiologies of human HCC as well as mouse HCC, with particular emphasis on ncRNAs distant from protein-coding genes. We find thousands of significantly up-regulated distal ncRNAs in HCC tumors compared to their matched non-tumors, which are as many as protein-coding genes. Moreover, we identify many LTR retroviral promoters activated in HCC tissues and expressed in a subfamily-specific manner, which account for approximately 20% of the up-regulated distal ncRNAs. The transcripts derived from LTRs, determined by 3' RACE, are multi-exon nuclear ncRNAs typically 0.5-2kb in length. This study sheds light on ncRNA transcriptome of human and mouse HCC. Expression profiles using CAGE for 37 mouse HCC. The human data are archived at dbGaP (phs000885.v1.p1). An umbrella BioProject has been created to associate the GEO and dbGaP BioProjects: PRJNA278792

2015-09-10 | E-GEOD-60982 | biostudies-arrayexpress

Strong Activation of Retroviral LTRs in HCC

Project description:<p>The ncRNA transcriptome of human hepatocellular carcinoma (HCC) is largely unexplored. We used CAGE to characterize transcription start sites across different etiologies of human HCCs with emphasis on ncRNAs. Here we report that retroviral LTR promoters, expressed in healthy tissues such as testis and placenta but not liver, are widely activated in HCC. Despite HCC heterogeneity, a subset of LTR-derived ncRNAs were more than 10-fold up-regulated in the vast majority of samples. HCCs with a high LTR activity mostly had a viral etiology, were less differentiated and showed higher risk of recurrence. CAGE enabled us to build a promoter map for HCC, which uncovers a new layer of complexity in HCC genomics.</p>

| phs000885 | dbGaP

Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and in trans effects on the protein regulatory network

Project description:Non-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts.

2021-01-19 | E-MTAB-9956 | biostudies-arrayexpress

Unexpected diversity of chloroplast non-coding RNAs as revealed by deep sequencing of the Arabidopsis transcriptome

Project description:Non-coding RNAs (ncRNAs) are widely expressed in both prokaryotes and eukaryotes. Eukaryotic ncRNAs are commonly small (18-25 nt) micro- and small interfering RNAs involved in post-transcriptional gene silencing, while prokaryotic ncRNAs vary in size and are involved in various aspects of gene regulation. Given the prokaryotic origin of organelles, the presence of ncRNAs might be expected, however, the full spectrum of organellar ncRNAs has not been determined systematically. Here, strand-specific RNA-Seq analysis was used to identify 107 candidate ncRNAs from Arabidopsis thaliana chloroplasts, primarily encoded opposite protein- coding and tRNA genes. Forty-eight ncRNAs were shown to accumulate by RNA gel blot as discrete transcripts in wild-type (WT) plants and/or the pnp1-1 mutant, which lacks the chloroplast ribonuclease polynucleotide phosphorylase (cpPNPase). Ninety-eight percent of the ncRNAs detected by RNA gel blot had different transcript patterns between WT and pnp1-1, suggesting cpPNPase has a significant role in chloroplast ncRNA biogenesis and accumulation. Analysis of materials deficient for other major chloroplast ribonucleases, RNase R, RNase E and RNase J, showed differential effects on ncRNA accumulation and/or form, suggesting specificity in RNase-ncRNA interactions. 5' end mapping showed that some ncRNAs are transcribed from dedicated promoters, while others result from transcriptional read-through. Finally, correlations between accumulation of some ncRNAs and the symmetrically-transcribed sense RNA are consistent with a role in RNA stability. Overall, our data suggest that this extensive population of ncRNAs has the potential to underpin a previously underappreciated regulatory mode in the chloroplast.

2011-10-13 | E-MTAB-4478 | biostudies-arrayexpress

P-TEFb function in ncRNA transcription

Project description:Many ncRNAs serve as regulatory molecules in various physiological pathways. Distinct from protein-coding RNA expression, ncRNA expression is regulated solely by transcription and RNA processing/stability. Transcriptional regulation in ncRNA genes is thus important to be understood and is yet to be known completely. Previously, we identified that a subset of mammalian ncRNA genes is transcriptionally regulated by RNA Pol II promoter-proximal pausing and in a tissue-specific manner. In this study, human stimulus-inducible ncRNA genes were monitored to assess the function of P-TEFb, a master Pol II pausing regulator for protein-coding genes, in ncRNA transcription. Our findings indicate that the expression of many ncRNA genes is regulated by P-TEFb. Interestingly, a biphasic characteristic of P-TEFb inhibition in serum responsive ncRNA genes was observed: S2 phospho-Pol II was largely increased in the TSS (–300 to +300) whereas overall, it was decreased in the gene body (> +350) upon chemical inhibition of P-TEFb. In addition, the three representative ncRNAs, MALAT1, NEAT1, and XIST, were further analyzed for determining P-TEFb association. Taken together, we propose the transcriptional activation of many human ncRNAs utilizing pausing and releasing Pol II and the regulatory mechanism of transcriptional elongation of these genes requiring the function of P-TEFb.

2018-07-31 | GSE117848 | GEO

Tissue specific expression of non-coding RNAs

Project description:Thousands of novel non-coding RNAs (ncRNA) has been identified in recent years. Only few have been functionally characterized and it is thus unclear which and how many are functional. Here, we characterize expression of ncRNAs in twelve human tissues using a costum designed microarray. The study serve as a first analysis to gain further insight into expression behavior of a broad and comprehensive collection of ncRNAs and pinpoint a set of ncRNAs we believe are functional. Expression was measured in triplicates of twelve human tissues using a custom-designed array containing 26,910 non-coding RNA features and a set of 6,856 protein-coding genes.

2013-06-01 | E-GEOD-41947 | biostudies-arrayexpress

Small RNA mediated DNA (cytosine-5) methyltransferase 1 inhibition leads to aberrant DNA methylation

Project description:Mammalian cells contain copious amounts of RNA including both coding and non-coding RNA (ncRNA). Generally the ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level. Among ncRNA, the long ncRNA and small ncRNA can affect histone modification, DNA methylation targeting and gene silencing. Here we show that endogenous DNA methyltransferase 1 (DNMT1) co-purifies with inhibitory ncRNAs. MicroRNAs (miRNAs) binds directly to DNMT1 with high affinity. The binding of miRNAs, such as miR-155, leads to inhibition of DNMT1 enzyme activity. Exogenous miR-155 in cells induces aberrant DNA methylation of the genome, resulting in hypomethylation of low to moderately methylated regions. And small shift of hypermethylation of previously hypomethylated region was also observed. Furthermore, hypomethylation led to activation of genes. Based on these observations, we propose that overexpression of specific miRNAs in human cancer may lead to aberrant DNA methylation and altered gene-expression. Examine of the DNA methylation and mRNA profile of HCT 116 cells transfected by random 23-mer or miR-155 RNA

2015-04-21 | E-GEOD-68027 | biostudies-arrayexpress

Small RNA mediated DNA (cytosine-5) methyltransferase 1 inhibition leads to aberrant DNA methylation

2015-04-21 | GSE68027 | GEO

Ameloblastoma RNA profiling uncovers a distinct non-coding RNA signature

Project description:Ameloblastoma of the jaws remains the top difficult to treat odontogenic tumour and has a high recurrence rate. New evidence suggests that non-coding RNAs (ncRNAs) play a critical role in tumour genesis and prognosis of cancer. However, ameloblastoma ncRNA expression data is lacking. Here we present the first report of ameloblastoma ncRNA signatures. A total of 95 ameloblastoma cases and a global array transcriptome technology covering > 285.000 full-length transcripts were used in this two-step analysis. The analysis first identified in a test cohort 31 upregulated ameloblastoma-associated ncRNAs accompanied by signalling pathways of cancer, spliceosome, mRNA surveillance and Wnt. Further validation in an independent cohort points out the long non-coding (lncRNAs) and small nucleolar RNA (snoRNAs): LINC340, LINC342, SNORD116-25, SNORA11, SNORA21, SNORA47 and SNORA65 as a distinct ncRNA signature of ameloblastoma. Importantly, the presence of these ncRNAs was independent of BRAF-V600E and SMO-L412F mutations, histology type or tumour location, but was positively correlated with the tumour size. Taken together, this study shows a systematic investigation of ncRNA expression of ameloblastoma, and illuminates new diagnostic and therapeutic targets for this invasive odontogenic tumour.

2017-03-01 | GSE90518 | GEO

A novel protein coding potential of long intergenic non-coding RNAs (lincRNAs) in the kinetoplastid protozoan parasite Leishmania major

Project description:Leishmania major is a kinetoplastid protozoan parasite which causes the debilitating infectious disease cutaneous leishmaniasis (CL). This disease results in scars and disfiguration of the infected individuals. The L. major genome was the first leishmanial genome to be sequenced in 2005 and this study resulted in the identification of 8,300 protein coding genes. This landmark study paved the way for further sequencing of other leishmanial parasites (L. infantum, L. braziliensis and L. donovani). A recent study provided the glimpse of the global transcriptome of L. major promastigotes. This study identified 1,884 uniquely expressed non-coding RNAs (ncRNA) in L. major. Additionally, we had previously mapped the global proteome of L. major promastigote using a proteogenomic approach which resulted in identification of 3,613 proteins in L. major promastigotes which covered 43% of its proteome. In the present study, we have carried out extensive analysis of the 1,884 novel ncRNAs using a proteogenomic approach to identify their protein coding potential. Our analysis resulted in identification of 10 novel protein coding genes based on peptide data and additional hundreds of proteins coding genes based on homology searches of previously classified ncRNA genes. We have analyzed each of these novel protein coding genes and in the process have improved the genome annotation of L. major on the basis of mass spectrometry derived peptide data and also based on homology.

2016-05-11 | PXD002465 | Pride

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