Abstract 1057: Characterization of methylation patterns in cancer tissue shown by targeted Next-Gen bisulfite sequencing

Author(s):  
Jessica Alexander ◽  
Ryan Drennan ◽  
Ann Meyer ◽  
Jessica Xu ◽  
Matthew L. Poulin ◽  
...  
2018 ◽  
Vol 2018 ◽  
pp. 1-19 ◽  
Author(s):  
Zhen Wei ◽  
Subbarayalu Panneerdoss ◽  
Santosh Timilsina ◽  
Jingting Zhu ◽  
Tabrez A. Mohammad ◽  
...  

Background. Compared with the well-studied 5-methylcytosine (m5C) in DNA, the role and topology of epitranscriptome m5C remain insufficiently characterized. Results. Through analyzing transcriptome-wide m5C distribution in human and mouse, we show that the m5C modification is significantly enriched at 5′ untranslated regions (5′UTRs) of mRNA in human and mouse. With a comparative analysis of the mRNA and DNA methylome, we demonstrate that, like DNA methylation, transcriptome m5C methylation exhibits a strong clustering effect. Surprisingly, an inverse correlation between mRNA and DNA m5C methylation is observed at CpG sites. Further analysis reveals that RNA m5C methylation level is positively correlated with both RNA expression and RNA half-life. We also observed that the methylation level of mitochondrial RNAs is significantly higher than RNAs transcribed from the nuclear genome. Conclusions. This study provides an in-depth topological characterization of transcriptome-wide m5C modification by associating RNA m5C methylation patterns with transcriptional expression, DNA methylations, RNA stabilities, and mitochondrial genome.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chaitanya Erady ◽  
Adam Boxall ◽  
Shraddha Puntambekar ◽  
N. Suhas Jagannathan ◽  
Ruchi Chauhan ◽  
...  

AbstractUncharacterized and unannotated open-reading frames, which we refer to as novel open reading frames (nORFs), may sometimes encode peptides that remain unexplored for novel therapeutic opportunities. To our knowledge, no systematic identification and characterization of transcripts encoding nORFs or their translation products in cancer, or in any other physiological process has been performed. We use our curated nORFs database (nORFs.org), together with RNA-Seq data from The Cancer Genome Atlas (TCGA) and Genotype-Expression (GTEx) consortiums, to identify transcripts containing nORFs that are expressed frequently in cancer or matched normal tissue across 22 cancer types. We show nORFs are subject to extensive dysregulation at the transcript level in cancer tissue and that a small subset of nORFs are associated with overall patient survival, suggesting that nORFs may have prognostic value. We also show that nORF products can form protein-like structures with post-translational modifications. Finally, we perform in silico screening for inhibitors against nORF-encoded proteins that are disrupted in stomach and esophageal cancer, showing that they can potentially be targeted by inhibitors. We hope this work will guide and motivate future studies that perform in-depth characterization of nORF functions in cancer and other diseases.


2017 ◽  
Vol 27 (9) ◽  
pp. 1589-1596 ◽  
Author(s):  
Carine Legrand ◽  
Francesca Tuorto ◽  
Mark Hartmann ◽  
Reinhard Liebers ◽  
Dominik Jacob ◽  
...  

2019 ◽  
Vol 29 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Einstein Gnanatheepam ◽  
Udayakumar Kanniyappan ◽  
Koteeswaran Dornadula ◽  
Aruna Prakasarao ◽  
Ganesan Singaravelu

2020 ◽  
Vol 21 (S8) ◽  
Author(s):  
Antonino Fiannaca ◽  
Laura La Paglia ◽  
Massimo La Rosa ◽  
Riccardo Rizzo ◽  
Alfonso Urso

Abstract Background Non-coding RNAs include different classes of molecules with regulatory functions. The most studied are microRNAs (miRNAs) that act directly inhibiting mRNA expression or protein translation through the interaction with a miRNAs-response element. Other RNA molecules participate in the complex network of gene regulation. They behave as competitive endogenous RNA (ceRNA), acting as natural miRNA sponges to inhibit miRNA functions and modulate the expression of RNA messenger (mRNA). It became evident that understanding the ceRNA–miRNA–mRNA crosstalk would increase the functional information across the transcriptome, contributing to identify new potential biomarkers for translational medicine. Results We present miRTissue ce, an improvement of our original miRTissue web service. By introducing a novel computational pipeline, miRTissue ce provides an easy way to search for ceRNA interactions in several cancer tissue types. Moreover it extends the functionalities of previous miRTissue release about miRNA-target interaction in order to provide a complete insight about miRNA mediated regulation processes. miRTissue ce is freely available at http://tblab.pa.icar.cnr.it/mirtissue.html. Conclusions The study of ceRNA networks and its dynamics in cancer tissue could be applied in many fields of translational biology, as the investigation of new cancer biomarker, both diagnostic and prognostic, and also in the investigation of new therapeutic strategies of intervention. In this scenario, miRTissue ce can offer a powerful instrument for the analysis and characterization of ceRNA-ceRNA interactions in different tissue types, representing a fundamental step in order to understand more complex regulation mechanisms.


2007 ◽  
Vol 19 (1) ◽  
pp. 190
Author(s):  
N. T. D'Cruz ◽  
K. J. Wilson ◽  
M. K. Holland

Clinical and laboratory-assisted reproductive techniques such as ICSI have recently been associated with an increased incidence of several syndromes associated with defects in genomic imprinting. Genomically imprinted genes are expressed from only one parental allele and act to regulate growth of the fetus and placenta and brain development/ function. Imprinted genes are controlled by differentially methylated regions (DMRs), whereby one parental allelle (i.e. either maternal or paternal) is epigenetically silenced via methylation. Studies conducted in vitro suggest that culture of embryos and embryo manipulations may perturb the imprinting process. In the current study, the genomic DNA methylation patterns of CpG islands within bovine H19 (27 CpGs analyzed), Impact (36 CpGs), NDN (22 CpGs), and Xist (21 CpGs) were analyzed by bisulfite sequencing. Genomic DNA from a female fibroblast cell line and sperm were chosen for analysis. Potential DMRs for the 4 genes were identified, and semi-nested PCR primers were designed surrounding those regions. Second-round PCR products (2 separate reactions) were mixed, subcloned, and sequenced (n ≥ 10). The fibroblast methylation pattern of the Xist DMR showed consistent methylation in 50% of sequenced clones, with no methylation observed in sperm. The H19 DMR in fibroblast DNA also showed consistent methylation in 25% of sequenced clones, with sperm DNA fully methylated. These results confirm previous studies showing that Xist and H19 are imprinted in cattle. Sequencing of the putative Impact DMR clones indicated no methylation in either cell type, suggesting no imprinting in cattle, tissue-specific imprinting, or that this CpG island (15 bp post ATG) is not the DMR that controls imprinted expression of the Impact gene. The NDN DMR (500 bp post ATG) in sperm was not methylated, whereas the fibroblast cells had a variable methylation pattern. This may be for the same reasons suggested for Impact, but the variability within the CpG island may also be due to in vitro culture conditions resulting in aberrant methylation. This possible culture effect is currently being confirmed through bisulfite sequencing of the gene in an adult tissue. The investigation of methylation patterns in oocytes is also underway. Together, the information gathered will be used to determine the imprinting status of several bovine genes and, in the future, whether any of these imprinted genes are responsible for the increased pregnancy loss and calf abnormalities associated with advanced reproductive technologies.


Sign in / Sign up

Export Citation Format

Share Document