scholarly journals Human Endogenous Retroviruses in Glioblastoma Multiforme

2021 ◽  
Vol 9 (4) ◽  
pp. 764
Author(s):  
Zihao Yuan ◽  
Yuntao Yang ◽  
Ningyan Zhang ◽  
Claudio Soto ◽  
Xiaoqian Jiang ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Repetitive Elements ◽  
Endogenous Retroviruses ◽  
Differentially Expressed ◽  
P Value ◽  
Normal Brain ◽  
Sequencing Data ◽  
Significant Differential Expression ◽  
Human Endogenous Retroviruses ◽  
Brain Tissues

Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor. It is primarily diagnosed in the elderly and has a 5-year survival rate of less than 6% even with the most aggressive therapies. The lack of biomarkers has made the development of immunotherapy for GBM challenging. Human endogenous retroviruses (HERVs) are a group of viruses with long terminal repeat (LTR) elements, which are believed to be relics from ancient viral infections. Recent studies have found that those repetitive elements play important roles in regulating various biological processes. The differentially expressed LTR elements from HERVs are potential biomarkers for immunotherapy to treat GBM. However, the understanding of the LTR element expression in GBM is greatly lacking. Methods: We obtained 1077.4 GB of sequencing data from public databases. These data were generated from 111 GBM tissue studies, 30 GBM cell lines studies, and 45 normal brain tissues studies. We analyzed repetitive elements that were differentially expressed in GBM and normal brain samples. Results: We found that 48 LTR elements were differentially expressed (p-value < 0.05) between GBM and normal brain tissues, of which 46 were HERV elements. Among these 46 elements, 34 significantly changed HERVs belong to the ERV1 superfamily. Furthermore, 43 out of the 46 differentially expressed HERV elements were upregulated. Conclusion: Our results indicate significant differential expression of many HERV LTR elements in GBM and normal brain tissues. Expression levels of these elements could be developed as biomarkers for GBM treatments.

scholarly journals Computational analysis and verification of molecular genetic targets for glioblastoma

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Liang Xue ◽  
Haibing Liu ◽  
Yehuang Chen ◽  
Liangfeng Wei ◽  
Jingfang Hong
Keyword(s):  
Target Genes ◽  
Statistical Significance ◽  
Molecular Genetic ◽  
Specific Treatment ◽  
Disease Free Survival ◽  
Differentially Expressed ◽  
P Value ◽  
Normal Brain ◽  
Hub Genes ◽  
Brain Tissues

Abstract Background: Glioblastoma (GBM) is the most common malignant brain tumor with a poor prognosis. The initial treatment for high-grade gliomas is surgical excision. However, even with concomitant use of radiation or chemotherapy, patients are still prone to recurrence. The specific pathogenesis of GBM is still controversial. Methods: Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between GBM and normal brain tissues were screened. P-value was obtained by Bayes test based on the limma package. Statistical significance was set as P-value &lt;0.05 and |Fold change (FC)| &gt; 0.2 (GSE90886); P-value &lt;0.05 and |FC| &gt; 1 (GSE116520, GSE103228). Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) network were performed. Hub genes were selected from miRNA target genes and DEGs. GBM and normal brain tissues were extracted to verify the expression. Results: A total of 100 DEGs were overlapped in both datasets. Analysis of pathways and process enrichment tests indicated that ion transport, positive regulation of macromolecule metabolic process, cell cycle, axon guidance were enriched in the GBM. Sixteen hub genes were identified. Hub genes ADARB1 and neuropilin 1 (NRP1) were significantly associated with overall survival (OS) and disease-free survival (DFS) (P&lt;0.05). Eukaryotic translation termination factor 1 (ETF1) was associated with DFS (P&lt;0.05). Conclusions: DEGs and DEMs were found between GBM tumor tissues and normal brain tissues. These biomarkers may be used as targets for early diagnosis and specific treatment.

scholarly journals Integration of mRNA and miRNA Analysis Reveals the Molecular Mechanism of Cotton Response to Salt Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing Zhan ◽  
Yangyang Diao ◽  
Guo Yin ◽  
Muhammad Sajjad ◽  
Xi Wei ◽  
...  
Keyword(s):  
Salt Stress ◽  
Differential Expression ◽  
Signal Transduction Pathway ◽  
Differentially Expressed ◽  
Sequencing Data ◽  
Regulatory Relationship ◽  
Significant Differential Expression ◽  
Amplification Bias ◽  
Before And After ◽  
Increased Sensitivity

To identify the regulatory network of known and novel microRNAs (miRNAs) and their targets responding to salt stress, a combined analysis of mRNA libraries, small RNA libraries, and degradome libraries were performed. In this study, we used unique molecular identifiers (UMIs), which are more sensitive, accurate, and reproducible than traditional methods of sequencing, to quantify the number of molecules and correct for amplification bias. We identified a total of 312 cotton miRNAs using seedlings at 0, 1, 3, and 6 h after NaCl treatment, including 80 known ghr-miRNAs and 232 novel miRNAs and found 155 miRNAs that displayed significant differential expression under salt stress. Among them, fifty-nine differentially expressed miRNAs were simultaneously induced in two or three tissues, while 66, 11, and 19 were specifically expressed in the roots, leaves, and stems, respectively. It is indicated there were different populations of miRNAs against salt stress in roots, leaves and stems. 399 candidate targets of salt-induced miRNAs showed significant differential expression before and after salt treatment, and 72 targets of 25 miRNAs were verified by degradome sequencing data. Furthermore, the regulatory relationship of miRNA-target gene was validated experimentally via 5′RLM-RACE, proving our data reliability. Gene ontology and KEGG pathway analysis found that salt-responsive miRNA targets among the differentially expressed genes were significantly enriched, and mainly involved in response to the stimulus process and the plant hormone signal transduction pathway. Furthermore, the expression levels of newly identified miRNA mir1 and known miRNAs miR390 and miR393 gradually decreased when subjected to continuous salt stress, while overexpression of these miRNAs both increased sensitivity to salt stress. Those newly identified miRNAs and mRNA pairs were conducive to genetic engineering and better understanding the mechanisms responding to salt stress in cotton.

scholarly journals Schizophrenia risk from locus-specific human endogenous retroviruses

2019 ◽  
Author(s):  
Rodrigo R.R. Duarte ◽  
Matthew L. Bendall ◽  
Miguel de Mulder ◽  
Christopher E. Ormsby ◽  
Greta A. Beckerle ◽  
...  
Keyword(s):  
Association Studies ◽  
Endogenous Retroviruses ◽  
Substantial Contribution ◽  
Genome Wide Association Studies ◽  
Sequencing Data ◽  
Human Endogenous Retroviruses ◽  
Risk Variants ◽  
Repetitive Nature ◽  
Common Genetic Variants ◽  
Dorsolateral Prefrontal

AbstractSchizophrenia genome-wide association studies highlight the substantial contribution of risk attributed to the non-coding genome where human endogenous retroviruses (HERVs) are encoded. These ancient viral elements have previously been overlooked in genetic and transcriptomic studies due to their poor annotation and repetitive nature. Using a new, comprehensive HERV annotation, we found that the fraction of the genome where HERVs are located (the ‘retrogenome’) is enriched for schizophrenia risk variants, and that there are 148 disparate HERVs involved in susceptibility. Analysis of RNA-sequencing data from the dorsolateral prefrontal cortex of 259 schizophrenia cases and 279 controls from the CommonMind Consortium showed that HERVs are actively expressed in the brain (n = 3,979), regulated in cis by common genetic variants (n = 1,759), and differentially expressed in patients (n = 81). Convergent analyses implicate LTR25_6q21 and ERVLE_8q24.3h as HERVs of etiological relevance to schizophrenia, which are co-regulated with genes involved in neuronal and mitochondrial function, respectively. Our findings provide a strong rationale for exploring the retrogenome and the expression of these locus-specific HERVs as novel risk factors for schizophrenia and potential diagnostic biomarkers and treatment targets.

Human Endogenous Retroviruses and Residues of Ancient Times - are Differentially Expressed in Crohǹs Disease

2017 ◽  
Vol 152 (5) ◽  
pp. S985
Author(s):  
Thomas Klag ◽  
Lioba Courth ◽  
Maureen J. Ostaff ◽  
German Ott ◽  
Eduard F. Stange ◽  
...  
Keyword(s):  
Endogenous Retroviruses ◽  
Differentially Expressed ◽  
Crohns Disease ◽  
Human Endogenous Retroviruses ◽  
Ancient Times

scholarly journals Lipid accumulation and oxidation in glioblastoma multiforme

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bouchra Taïb ◽  
Amine M. Aboussalah ◽  
Mohammed Moniruzzaman ◽  
Suming Chen ◽  
Norman J. Haughey ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Glioblastoma Multiforme ◽  
Lipid Droplets ◽  
Monounsaturated Fatty Acids ◽  
Acid Oxidation ◽  
Normal Brain ◽  
Lipid Species ◽  
Brain Tissues

AbstractGlioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tissues while undetectable in normal brain tissues, yet the identity and functions of lipid species in GBM are not well understood. The aims of the present work are to determine how GBM utilizes fatty acids, and assess their roles in GBM proliferation. Treatment of U138 GBM cells with a monounsaturated fatty acid, oleic acid, induces accumulation of perilipin 2-coated lipid droplets containing triglycerides enriched in C18:1 fatty acid, and increases fatty acid oxidation. Interestingly, oleic acid also increases glucose utilization and proliferation of GBM cells. In contrast, pharmacologic inhibition of monoacylglycerol lipase attenuates GBM proliferation. Our findings demonstrate that monounsaturated fatty acids promote GBM proliferation via triglyceride metabolism, suggesting a novel lipid droplet-mediated pathway which may be targeted for GBM treatment.

scholarly journals 12 Survival-related differentially expressed genes based on the TARGET-osteosarcoma database

2021 ◽  
pp. 153537022110074
Author(s):  
Emel Rothzerg ◽  
Jiake Xu ◽  
David Wood ◽  
Sulev Kõks
Keyword(s):  
Differentially Expressed Genes ◽  
Clinical Information ◽  
Differentially Expressed ◽  
P Value ◽  
Sequencing Data ◽  
Gene Expressions ◽  
Expression Of Genes ◽  
Kaplan Meier ◽  
And Gender ◽  
Upregulated Genes

The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project aims to determine molecular changes that drive childhood cancers, including osteosarcoma. The main purpose of the program is to use the open-source database to develop novel, effective, and less toxic therapies. We downloaded TARGET-OS RNA-Sequencing data through R studio and merged the mRNA expression of genes with clinical information (vital status, survival time and gender). Further, we analyzed differential gene expressions between dead and alive patients based on TARGET-OS project. By this study, we found 5758 differentially expressed genes between deceased and alive patients with a false discovery rate below 0.05; 4469 genes were upregulated in deceased patients compared to alive, whereas 1289 genes were downregulated. The survival-related genes were obtained using Kaplan–Meier survival analysis and Cox univariate regression (KM < 0.05 and Cox P-value < 0.05). Out of 5758 differentially expressed genes, only 217 have been associated with overall survival. Eight survival-related downregulated genes ( ERCC4, CLUAP1, CTNNBIP1, GCA, RAB40C, SIRPA, USP11, and TCN2) and four survival-related upregulated genes ( MUC1, COL13A1, JAG2 and KAZALD1) were selected for further analysis as potential independent prognostic candidate genes. This study may help to discover novel prognostic markers and potential therapeutic targets for osteosarcoma.

scholarly journals An Integrative Transcriptomic and Methylation Approach for Identifying Differentially Expressed Circular RNAs Associated with DNA Methylation Change

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 657
Author(s):  
Tianyi Xu ◽  
LiPing Wang ◽  
Peilin Jia ◽  
Xiaofeng Song ◽  
Zhongming Zhao
Keyword(s):  
Dna Methylation ◽  
Rank Order ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
P Value ◽  
General View ◽  
Methylation Change ◽  
Sequencing Data ◽  
Genome Wide

Recently, accumulating evidence has supported that circular RNA (circRNA) plays important roles in tumorigenesis by regulating gene expression at transcriptional and post-transcriptional levels. Expression of circRNAs can be epigenetically silenced by DNA methylation; however, the underlying regulatory mechanisms of circRNAs by DNA methylation remains largely unknown. We explored this regulation in hepatocellular carcinoma (HCC) using genome-wide DNA methylation and RNA sequencing data of the primary tumor and matched adjacent normal tissues from 20 HCC patients. Our pipeline identified 1012 upregulated and 747 downregulated circRNAs (collectively referred to as differentially expressed circRNAs, or DE circRNAs) from HCC RNA-seq data. Among them, 329 DE circRNAs covered differentially methylated sites (adjusted p-value < 0.05, |ΔM| > 0.5) in circRNAs’ interior and/or flanking regions. Interestingly, the corresponding parental genes of 46 upregulated and 31 downregulated circRNAs did not show significant expression change in the HCC tumor versus normal samples. Importantly, 34 of the 77 DE circRNAs (44.2%) had significant correlation with DNA methylation change in HCC (Spearman’s rank-order correlation, p-value < 0.05), suggesting that aberrant DNA methylation might regulate circular RNA expression in HCC. Our study revealed genome-wide differential circRNA expression in HCC. The significant correlation with DNA methylation change suggested that epigenetic regulation might act on both mRNA and circRNA expression. The specific regulation in HCC and general view in other cancer or disease requires further investigation.

scholarly journals Diverse endogenous retroviruses generate structural variation between human genomes via LTR recombination

2018 ◽  
Author(s):  
Jainy Thomas ◽  
Hervé Perron ◽  
Cédric Feschotte
Keyword(s):  
Structural Variation ◽  
Genomic Variation ◽  
Endogenous Retroviruses ◽  
Interindividual Variation ◽  
Sequencing Data ◽  
Long Terminal Repeats ◽  
Substantial Fraction ◽  
Human Endogenous Retroviruses ◽  
Solo Ltrs ◽  
Human Genomes

ABSTRACTHuman endogenous retroviruses (HERVs) occupy a substantial fraction of the genome and impact cellular function with both beneficial and deleterious consequences. The vast majority of HERV sequences descend from ancient retroviral families no longer capable of infection or genomic propagation. In fact, most are no longer represented by full-length proviruses but by solitary long terminal repeats (solo LTRs) that arose via non-allelic recombination events between the two LTRs of a proviral insertion. Because LTR-LTR recombination events may occur long after proviral insertion but are challenging to detect in resequencing data, we hypothesize that this mechanism produces an underappreciated amount of genomic variation in the human population. To test this idea, we develop a computational pipeline specifically designed to capture such dimorphic HERV alleles from short-read genome sequencing data. When applied to 279 individuals sequenced as part of the Simons Genome Diversity Project, the pipeline retrieves most of the dimorphic variants previously reported for the HERV-K(HML2) subfamily as well as dozens of additional candidates, including members of the HERV-H and HERV-W families. We experimentally validate several of these candidates, including the first reported instance of an unfixed HERV-W provirus. These data indicate that human proviral content exhibit more extensive interindividual variation than previously recognized. These findings have important implications for our understanding of the contribution of HERVs to human physiology and disease.

scholarly journals TET2 as a tumor suppressor and therapeutic target in T-cell acute lymphoblastic leukemia

2021 ◽  
Vol 118 (34) ◽  
pp. e2110758118
Author(s):  
Maike Bensberg ◽  
Olof Rundquist ◽  
Aida Selimović ◽  
Cathrine Lagerwall ◽  
Mikael Benson ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Endogenous Retroviruses ◽  
Sequencing Data ◽  
Human Endogenous Retroviruses ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Normal Human ◽  
T Cell Malignancies

Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy resulting from overproduction of immature T-cells in the thymus and is typified by widespread alterations in DNA methylation. As survival rates for relapsed T-ALL remain dismal (10 to 25%), development of targeted therapies to prevent relapse is key to improving prognosis. Whereas mutations in the DNA demethylating enzyme TET2 are frequent in adult T-cell malignancies, TET2 mutations in T-ALL are rare. Here, we analyzed RNA-sequencing data of 321 primary T-ALLs, 20 T-ALL cell lines, and 25 normal human tissues, revealing that TET2 is transcriptionally repressed or silenced in 71% and 17% of T-ALL, respectively. Furthermore, we show that TET2 silencing is often associated with hypermethylation of the TET2 promoter in primary T-ALL. Importantly, treatment with the DNA demethylating agent, 5-azacytidine (5-aza), was significantly more toxic to TET2-silenced T-ALL cells and resulted in stable re-expression of the TET2 gene. Additionally, 5-aza led to up-regulation of methylated genes and human endogenous retroviruses (HERVs), which was further enhanced by the addition of physiological levels of vitamin C, a potent enhancer of TET activity. Together, our results clearly identify 5-aza as a potential targeted therapy for TET2-silenced T-ALL.

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