scholarly journals Recurrently deregulated lncRNAs associated with HCC tumorigenesis and metastasis revealed by genomic, epigenomic, and transcriptomic profiling in paired primary tumor and PVTT samples

2016 ◽  
Author(s):  
Yang Yang ◽  
Lei Chen ◽  
Jin Gu ◽  
Hanshuo Zhang ◽  
Jiapei Yuan ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Expression Patterns ◽  
Copy Number Variations ◽  
Intrahepatic Metastasis ◽  
Clinical Samples ◽  
Loss Of Function ◽  
Specific Expression ◽  
Cancer Data ◽  
Novel Biomarkers

AbstractHepatocellular carcinoma (HCC) are highly potent to invade the portal venous system and subsequently develop into the portal vein tumor thrombosis (PVTT). PVTT could induce intrahepatic metastasis, which is closely associated with poor prognosis. A comprehensive systematic characterization of long noncoding RNAs (lncRNAs) associated with HCC metastasis has not been reported. Here, we first assayed 60 clinical samples (matched primary tumor, adjacent normal tissue, and PVTT) from 20 HCC patients using total RNA sequencing. We identified and characterized 8,603 novel lncRNAs from 9.6 billion sequenced reads, indicating specific expression of these lncRNAs in our samples. On the other hand, the expression patterns of 3,212 known and novel recurrently deregulated lncRNAs (in >=20% of our patients) were well correlated with clinical data in a TCGA cohort and published liver cancer data. Some lncRNAs (e.g., RP11-166D19.1/MIR100HG) were shown to be useful as putative biomarkers for prognosis and metastasis. Moreover, matched array data from 60 samples showed that copy number variations (CNVs) and alterations in DNA methylation contributed to the observed recurrent deregulation of 716 lncRNAs. Subsequently, using a coding-noncoding co-expression network, we found that many recurrently deregulated lncRNAs were enriched in clusters of genes related to cell adhesion, immune response, and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. The results of our integrative analysis provide a valuable resource regarding functional lncRNAs and novel biomarkers associated with HCC tumorigenesis and metastasis.

Cloning and Characterization of EphA3 (Hek) Gene Promoter: DNA Methylation Regulates Expression in Hematopoietic Tumor Cells

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2477-2486 ◽  
Author(s):  
Mirella Dottori ◽  
Michelle Down ◽  
Andreas Hüttmann ◽  
David R. Fitzpatrick ◽  
Andrew W. Boyd
Keyword(s):  
Dna Methylation ◽  
Cell Lines ◽  
Tyrosine Kinases ◽  
Expression Patterns ◽  
Gene Promoter ◽  
Restriction Enzymes ◽  
Clinical Samples ◽  
Cpg Dinucleotides ◽  
Normal Tissues

The Eph family of receptor tyrosine kinases (RTK) has restricted temporal and spatial expression patterns during development, and several members are also found to be upregulated in tumors. Very little is known of the promoter elements or regulatory factors required for expression of Eph RTK genes. In this report we describe the identification and characterization of the EphA3 gene promoter region. A region of 86 bp located at −348 bp to −262 bp upstream from the transcription start site was identified as the basal promoter. This region was shown to be active in both EphA3-expressing and -nonexpressing cell lines, contrasting with the widely different levels of EphA3 expression. We noted a region rich in CpG dinucleotides downstream of the basal promoter. Using Southern blot analyses with methylation-sensitive restriction enzymes and bisulfite sequencing of genomic DNA, sites of DNA methylation were identified in hematopoietic cell lines which correlated with their levels of EphA3 gene expression. We showed that EphA3 was not methylated in normal tissues but that a subset of clinical samples from leukemia patients showed extensive methylation, similar to that observed in cell lines. These results suggest that DNA methylation may be an important mechanism regulating EphA3 transcription in hematopoietic tumors.

scholarly journals scHLAcount: Allele-specific HLA expression from single-cell gene expression data

2019 ◽  
Author(s):  
Charlotte A. Darby ◽  
Michael J. T. Stubbington ◽  
Patrick J. Marks ◽  
Álvaro Martínez Barrio ◽  
Ian T. Fiddes
Keyword(s):  
Single Cells ◽  
Expression Patterns ◽  
Allelic Expression ◽  
Loss Of Function ◽  
Cell Type ◽  
Sequencing Data ◽  
Cell Type Specificity ◽  
Specific Expression ◽  
Hla Genes ◽  
Allele Specific

AbstractStudies in bulk RNA sequencing data suggest cell-type and allele-specific expression of the human leukocyte antigen (HLA) genes. These loci are extremely diverse and they function as part of the major histocompatibility complex (MHC) which is responsible for antigen presentation. Mutation and or misregulation of expression of HLA genes has implications in diseases, especially cancer. Immune responses to tumor cells can be evaded through HLA loss of function. However, bulk RNA-seq does not fully disentangle cell type specificity and allelic expression. Here we present scHLAcount, a workflow for computing allele-specific molecule counts of the HLA genes in single cells an individualized reference. We demonstrate that scHLAcount can be used to find cell-type specific allelic expression of HLA genes in blood cells, and detect different allelic expression patterns between tumor and normal cells in patient biopsies. scHLAcount is available at https://github.com/10XGenomics/scHLAcount.

scholarly journals Differential Regulation and Posttranslational Processing of the Class II Hydrophobin Genes from the Biocontrol Fungus Hypocrea atroviridis

2009 ◽  
Vol 75 (10) ◽  
pp. 3222-3229 ◽  
Author(s):  
Marianna Mikus ◽  
L�r�nt Hatvani ◽  
Torsten Neuhof ◽  
Monika Komoń-Zelazowska ◽  
Ralf Dieckmann ◽  
...  
Keyword(s):  
Vegetative Growth ◽  
Expression Patterns ◽  
Pathogenic Fungi ◽  
Class Ii ◽  
Carbon Starvation ◽  
Molecular Ions ◽  
Mechanical Injury ◽  
Extracellular Proteins ◽  
Loss Of Function ◽  
Specific Expression

ABSTRACT Hydrophobins are small extracellular proteins, unique to and ubiquitous in filamentous fungi, which mediate interactions between the fungus and environment. The mycoparasitic fungus Hypocrea atroviridis has recently been shown to possess 10 different class II hydrophobin genes, which is a much higher number than that of any other ascomycete investigated so far. In order to learn the potential advantage of this hydrophobin multiplicity for the fungus, we have investigated their expression patterns under different physiological conditions (e.g., vegetative growth), various conditions inducing sporulation (light, carbon starvation, and mechanical injury-induced stress), and confrontation with potential hosts for mycoparasitism. The results show that the 10 hydrophobins display different patterns of response to these conditions: one hydrophobin (encoded by hfb-2b) is constitutively induced under all conditions, whereas other hydrophobins were formed only under conditions of carbon starvation (encoded by hfb-1c and hfb-6c) or light plus carbon starvation (encoded by hfb-2c, hfb-6a, and hfb-6b). The hydrophobins encoded by hfb-1b and hfb-5a were primarily formed during vegetative growth and under mechanical injury-provoked stress. hfb-22a was not expressed under any conditions and is likely a pseudogene. None of the 10 genes showed a specific expression pattern during mycoparasitic interaction. Most, but not all, of the expression patterns under the three different conditions of sporulation were dependent on one or both of the two blue-light regulator proteins BLR1 and BLR2, as shown by the use of respective loss-of-function mutants. Matrix-assisted laser desorption ionization-time of flight mass spectrometry of mycelial solvent extracts provided sets of molecular ions corresponding to HFB-1b, HFB-2a, HFB-2b, and HFB-5a in their oxidized and processed forms. These in silico-deduced sequences of the hydrophobins indicate cleavages at known signal peptide sites as well as additional N- and C-terminal processing. Mass peaks observed during confrontation with plant-pathogenic fungi indicate further proteolytic attack on the hydrophobins. Our study illustrates both divergent and redundant functions of the 10 hydrophobins of H. atroviridis.

scholarly journals Circulating Long Non-Coding RNAs as Novel Potential Biomarkers for Osteogenic Sarcoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4214
Author(s):  
Sutpirat Moonmuang ◽  
Parunya Chaiyawat ◽  
Salinee Jantrapirom ◽  
Dumnoensun Pruksakorn ◽  
Luca Lo Piccolo
Keyword(s):  
Clinical Decision Making ◽  
Expression Patterns ◽  
Osteogenic Sarcoma ◽  
Clinical Decision ◽  
Diagnostic Tools ◽  
Liquid Biopsies ◽  
Specific Expression ◽  
Altered Expression ◽  
Novel Biomarkers ◽  
Non Coding Rnas

Circulating cell-free nucleic acids recently became attractive targets to develop non-invasive diagnostic tools for cancer detection. Along with DNA and mRNAs, transcripts lacking coding potential (non-coding RNAs, ncRNAs) directly involved in the process of tumor pathogenesis have been recently detected in liquid biopsies. Interestingly, circulating ncRNAs exhibit specific expression patterns associated with cancer and suggest their role as novel biomarkers. However, the potential of circulating long ncRNAs (c-lncRNAs) to be markers in osteosarcoma (OS) is still elusive. In this study we performed a systematic review to identify thirteen c-lncRNAs whose altered expression in blood associate with OS. We herein discuss the potential impact that these c-lncRNAs may have on clinical decision-making in the management of OS. Overall, we aimed to provide novel insights that can contribute to the development of future precision medicine in oncology.

scholarly journals Genome-wide identification, characterization and expression analysis of BES1 gene family in tomato

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Deding Su ◽  
Wei Xiang ◽  
Ling Wen ◽  
Wang Lu ◽  
Yuan Shi ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Patterns ◽  
Transcriptional Repressors ◽  
Promoter Regions ◽  
Specific Expression ◽  
Genome Wide ◽  
Development Processes ◽  
Genomic Characterization ◽  
Functional Features

Abstract Background As the key regulators in BR signaling, BES1 family genes regulate thousands of target genes involved in various development processes. So far, the functions of BES1 family are poorly understood in tomato, and a comprehensive genomic and expressional analysis is worth to conduct for this family. Results Here, nine SlBES1 family members were identified in tomato and classified into five groups based on the conserved motif, gene structure and phylogenetic analysis. Synteny among tomato, Arabidopsis, pepper and rice were further analyzed to obtain insights into evolutionary characteristics. Several cis-elements related to hormone, stress and plant development were exhibited in the promoter regions of SlBES1 family genes. Subcellular localization showed seven members localized both in the nucleus and cytoplasm, implying the presence of dephosphorylated and phosphorylated form of these seven proteins, furthermore, five of them possessed transcription activation activity whereas the left two functioned as transcriptional repressors. Another two members, however, neither localized in the nucleus nor had transactivation activity. Besides, SlBES1.8 showed flower-specific expression while other members expressed ubiquitously in all organs. Moreover, SlBES1 genes exhibited variational expression in response to nine principal plant hormones. Notably, the expression levels of SlBES1 genes presented a dominant downregulated trend in response to stresses. Conclusions In this study, we systematically analyzed the genomic characterization of SlBES1 family, together with the analyses of protein functional features and expression patterns, our results lay a foundation for the functional research of SlBES1 family.

scholarly journals Differential expression of H2A isoforms contribute to tissue and lineage specificity with HIST2H2AC as a potential cancer biomarker

2021 ◽  
Author(s):  
Sanket Girish Shah ◽  
Mudasir Rashid ◽  
Abhiram Natu ◽  
Sanjay Gupta
Keyword(s):  
Expression Patterns ◽  
Human Tumor ◽  
Tissue Type ◽  
Tumor Type ◽  
Histone H2a ◽  
Specific Expression ◽  
Cancer Data ◽  
Lineage Specificity ◽  
Specific Association ◽  
Tumor Types

AbstractRecent advancements in the field of histone biology imply non-redundancy in the function of histone H2A isoforms; however, the expression of H2A isoforms in various normal tissue types, the correlation among organs and tumor/tumor type-specific expression remain poorly investigated. The profiling of sixteen H2A isoforms in eleven different normal human tissue types strongly suggests their tissue-specific or predominant expression. Further, clustering analysis shows a lineage-specific correlation of H2A isoforms. In continuation, the expression analysis in twelve human tumor types shows overexpression of HIST2H2AC. Moreover, overexpression was observed exclusively in tumor samples but not with fetal samples; highlighting the cancer-specific association of HIST2H2AC. Further, in silico analysis of TCGA pan-cancer data also showed tumor-specific over-expression of the HIST2H2AC isoform. Our findings provide insights into tissue-type-specificity of histone H2A isoforms expression patterns and advance our understanding of their importance in lineage specification and cancer.

scholarly journals Transcriptome-based identification and expression characterization of RgABCC transporters in Rehmannia glutinosa

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253188
Author(s):  
Yan Hui Yang ◽  
Chao Jie Wang ◽  
Rui Fang Li ◽  
Yan Jie Yi ◽  
Lei Zeng ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Expression Patterns ◽  
Hormone Treatment ◽  
Rehmannia Glutinosa ◽  
Specific Expression ◽  
Physiological Processes ◽  
Specific Accumulation ◽  
Associated Proteins ◽  
Expression Characterization

ABCC multidrug resistance-associated proteins (ABCCs/MRPs), a subfamily of ABC transporters, are involved in multiple physiological processes. Although these proteins have been characterized in some plants, limited efforts have been made to address their possible roles in Rehmannia glutinosa, a medicinal plant. Here, we scanned R. glutinosa transcriptome sequences and identified 18 RgABCC genes by in silico analysis. Sequence alignment revealed that the RgABCCs were closely phylogenetically related and highly conserved with other plant ABCCs/MRPs. Subcellular localization revealed that most of the RgABCCs were deposited in vacuoles and a few in plasma membranes. Tissue-specific expression of the RgABCCs indicated significant specific accumulation patterns, implicating their roles in the respective tissues. Differential temporal expression patterns of the RgABCCs exhibited their potential roles during root development. Various abiotic stress and hormone treatment experiments indicated that some RgABCCs could be transcriptionally regulated in roots. Furthermore, the transcription of several RgABCCs in roots was strongly activated by cadmium (Cd), suggesting possible roles under heavy metal stresses. Functional analysis of RgABCC1 heterologous expression revealed that it may increase the tolerance to Cd in yeast, implying its Cd transport activity. Our study provides a detailed inventory and molecular characterization of the RgABCCs and valuable information for exploring their functions in R. glutinosa.

scholarly journals Transcriptome of the Deep-Sea Black Scabbardfish,Aphanopus carbo(Perciformes: Trichiuridae): Tissue-Specific Expression Patterns and Candidate Genes Associated to Depth Adaptation

2014 ◽  
Vol 2014 ◽  
pp. 1-21 ◽  
Author(s):  
Sergio Stefanni ◽  
Raul Bettencourt ◽  
Miguel Pinheiro ◽  
Gianluca De Moro ◽  
Lucia Bongiorni ◽  
...  
Keyword(s):  
Deep Sea ◽  
High Throughput Sequencing ◽  
Expression Patterns ◽  
Extreme Environments ◽  
Cdna Libraries ◽  
Sequencing Analysis ◽  
Specific Expression ◽  
Adaptation Processes ◽  
Sea Fish

Deep-sea fishes provide a unique opportunity to study the physiology and evolutionary adaptation to extreme environments. We carried out a high throughput sequencing analysis on a 454 GS-FLX titanium plate using unnormalized cDNA libraries from six tissues ofA. carbo. Assemblage and annotations were performed by Newbler and InterPro/Pfam analyses, respectively. The assembly of 544,491 high quality reads provided 8,319 contigs, 55.6% of which retrieved blast hits against the NCBI nonredundant database or were annotated with ESTscan. Comparison of functional genes at both the protein sequences and protein stability levels, associated with adaptations to depth, revealed similarities betweenA. carboand other bathypelagic fishes. A selection of putative genes was standardized to evaluate the correlation between number of contigs and their normalized expression, as determined by qPCR amplification. The screening of the libraries contributed to the identification of new EST simple-sequence repeats (SSRs) and to the design of primer pairs suitable for population genetic studies as well as for tagging and mapping of genes. The characterization of the deep-sea fishA. carbofirst transcriptome is expected to provide abundant resources for genetic, evolutionary, and ecological studies of this species and the basis for further investigation of depth-related adaptation processes in fishes.

scholarly journals Characterization of the Murine Alpha Interferon Gene Family

2004 ◽  
Vol 78 (15) ◽  
pp. 8219-8228 ◽  
Author(s):  
Vincent van Pesch ◽  
Hanane Lanaya ◽  
Jean-Christophe Renauld ◽  
Thomas Michiels
Keyword(s):  
Mouse Genome ◽  
Biological Activities ◽  
Expression Patterns ◽  
Alpha Interferon ◽  
Activity Levels ◽  
Specific Expression ◽  
Mouse Genome Sequence ◽  
Human Genomes ◽  
Interferon Gene

ABSTRACT Mouse and human genomes carry more than a dozen genes coding for closely related alpha interferon (IFN-α) subtypes. IFN-α, as well as IFN-β, IFN-κ, IFN-ε, and limitin, are thought to bind the same receptor, raising the question of whether different IFN subtypes possess specific functions. As some confusion existed in the identity and characteristics of mouse IFN-α subtypes, the availability of data from the mouse genome sequence prompted us to characterize the murine IFN-α family. A total of 14 IFN-α genes were detected in the mouse genome, in addition to three IFN-α pseudogenes. Four IFN-α genes (IFN-α1, IFN-α7/10, IFN-α8/6, and IFN-α11) exhibited surprising allelic divergence between 129/Sv and C57BL/6 mice. All IFN-α subtypes were found to be stable at pH 2 and to exhibit antiviral activity. Interestingly, some IFN subtypes (IFN-α4, IFN-α11, IFN-α12, IFN-β, and limitin) showed higher biological activity levels than others, whereas IFN-α7/10 exhibited lower activity. Most murine IFN-α turned out to be N-glycosylated. However, no correlation was found between N-glycosylation and activity. The various IFN-α subtypes displayed a good correlation between their antiviral and antiproliferative potencies, suggesting that IFN-α subtypes did not diverge primarily to acquire specific biological activities but probably evolved to acquire specific expression patterns. In L929 cells, IFN genes activated in response to poly(I•C) transfection or to viral infection were, however, similar.

scholarly journals Transcriptome-wide identification and characterization of WD40 genes, as well as their tissue-specific expression profiles and responses to heat stress in Dimocarpus longan Lour.

2021 ◽  
Vol 49 (1) ◽  
pp. 12191
Author(s):  
Wei ZHENG ◽  
Ziwei ZHANG ◽  
Xuefei YU ◽  
Tongtong XIE ◽  
Ning CHEN ◽  
...  
Keyword(s):  
Heat Stress ◽  
Abiotic Stresses ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Flavonoid Biosynthesis ◽  
Functional Verification ◽  
Specific Expression ◽  
Cis Acting ◽  
Qrt Pcr

The WD40 transcription factor (TF) family is widespread in plants and plays important roles in plant growth and development, transcriptional regulation, and tolerance to abiotic stresses. WD40 TFs have been identified and characterized in a diverse series of plant species. However, little information is available on WD40 genes from D. longan. In this study, a total of 45 DlWD40 genes were identified from D. longan RNA-Seq data, and further analysed by bioinformatics tools. Also, the expression patterns of DlWD40 genes in roots and leaves, as well as responses to heat stress, were evaluated using quantitative real-time PCR (qRT-PCR). We found that the 45 DlWD40 proteins, together with 80 WD40 proteins from Arabidopsis and Zea mays, could be categorized into six groups. Of these, the DlWD40-4 protein was highly homologous to Arabidopsis WDR5a, a protein participating in tolerance to abiotic stresses. Moreover, a total of 25 cis-acting elements, such as abiotic stress and flavonoid biosynthesis elements, were found in the promoters of DlWD40 genes. The DlWD40-33 gene is targeted by miR3627, which has been proposed to be involved in flavonoid biosynthesis. Using qRT-PCR, ten of the 45 DlWD40 genes were demonstrated to have diverse expression patterns between roots and leaves, and these ten DlWD40 genes could also respond to varying durations of a 38 °C heat stress in roots and leaves. The results reported here will provide a basis for the further functional verification of DlWD40 genes in D. longan.

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