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https://www.readbyqxmd.com/read/28938616/identification-of-potential-cancer-related-pseudogenes-in-lung-adenocarcinoma-based-on-cerna-hypothesis
#1
Yunzhen Wei, Zhiqiang Chang, Cheng Wu, Yinling Zhu, Kun Li, Yan Xu
Pseudogenes are initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. Far from being silent, pseudogenes are proved to regulate the expression of protein-coding genes through function as microRNA sponge in vivo. The aim of our study was to propose an integrative systems biology approach to identify disease pseudogenes base on competitive endogenous RNA (ceRNA) hypothesis. Here, we applied our method to lung adenocarcinoma (LUAD) RNASeq data from TCGA and identified 33 candidate pseudogenes...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938540/microrna-128-3p-regulates-mitomycin-c-induced-dna-damage-response-in-lung-cancer-cells-through-repressing-sptan1
#2
Rui Zhang, Chang Liu, Yahan Niu, Ying Jing, Haiyang Zhang, Jin Wang, Jie Yang, Ke Zen, Junfeng Zhang, Chen-Yu Zhang, Donghai Li
The DNA damage response is critical for maintaining genome integrity and preventing damage to DNA due to endogenous and exogenous insults. Mitomycin C (MMC), a potent DNA cross-linker, is used as a chemotherapeutic agent because it causes DNA inter-strand cross-links (DNA ICLs) in cancer cells. While many microRNAs, which may serve as oncogenes or tumor suppressors, are grossly dysregulated in human cancers, little is known about their roles in MMC-treated lung cancer. Here, we report that miR-128-3p can attenuate repair of DNA ICLs by targeting SPTAN1 (αII Sp), resulting in cell cycle arrest and promoting chromosomal aberrations in lung cancer cells treated with MMC...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938536/integrating-omics-data-and-protein-interaction-networks-to-prioritize-driver-genes-in-cancer
#3
Tiejun Zhang, Di Zhang
Although numerous approaches have been proposed to discern driver from passenger, identification of driver genes remains a critical challenge in the cancer genomics field. Driver genes with low mutated frequency tend to be filtered in cancer research. In addition, the accumulation of different omics data necessitates the development of algorithmic frameworks for nominating putative driver genes. In this study, we presented a novel framework to identify driver genes through integrating multi-omics data such as somatic mutation, gene expression, and copy number alterations...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938088/small-molecule-inhibitors-targeting-dna-repair-and-dna-repair-deficiency-in-research-and-cancer-therapy
#4
REVIEW
Sarah R Hengel, M Ashley Spies, Maria Spies
To maintain stable genomes and to avoid cancer and aging, cells need to repair a multitude of deleterious DNA lesions, which arise constantly in every cell. Processes that support genome integrity in normal cells, however, allow cancer cells to develop resistance to radiation and DNA-damaging chemotherapeutics. Chemical inhibition of the key DNA repair proteins and pharmacologically induced synthetic lethality have become instrumental in both dissecting the complex DNA repair networks and as promising anticancer agents...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28937943/multiomics-analysis-of-tumor-microenvironment-reveals-gata2-and-mirna-124-3p-as-potential-novel-biomarkers-in-ovarian-cancer
#5
Esra Gov, Medi Kori, Kazim Yalcin Arga
Ovarian cancer is a common and, yet, one of the most deadly human cancers due to its insidious onset and the current lack of robust early diagnostic tests. Tumors are complex tissues comprised of not only malignant cells but also genetically stable stromal cells. Understanding the molecular mechanisms behind epithelial-stromal crosstalk in ovarian cancer is a great challenge in particular. In the present study, we performed comparative analyses of transcriptome data from laser microdissected epithelial, stromal, and ovarian tumor tissues, and identified common and tissue-specific reporter biomolecules-genes, receptors, membrane proteins, transcription factors (TFs), microRNAs (miRNAs), and metabolites-by integration of transcriptome data with genome-scale biomolecular networks...
September 22, 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28937603/proteome-stability-as-a-key-factor-of-genome-integrity
#6
REVIEW
Sentiljana Gumeni, Zoi Evangelakou, Vassilis G Gorgoulis, Ioannis P Trougakos
DNA damage is constantly produced by both endogenous and exogenous factors; DNA lesions then trigger the so-called DNA damaged response (DDR). This is a highly synchronized pathway that involves recognition, signaling and repair of the damage. Failure to eliminate DNA lesions is associated with genome instability, a driving force in tumorigenesis. Proteins carry out the vast majority of cellular functions and thus proteome quality control (PQC) is critical for the maintenance of cellular functionality. PQC is assured by the proteostasis network (PN), which under conditions of proteome instability address the triage decision of protein fold, hold, or degrade...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28937589/viral-cellular-dna-junctions-as-molecular-markers-for-assessing-intra-tumor-heterogeneity-in-cervical-cancer-and-for-the-detection-of-circulating-tumor-dna
#7
Katrin Carow, Mandy Gölitz, Maria Wolf, Norman Häfner, Lars Jansen, Heike Hoyer, Elisabeth Schwarz, Ingo B Runnebaum, Matthias Dürst
The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV) DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined cervical cancer clonality in the context of intra-tumor heterogeneity. Moreover, we assessed the potential of these fragments as molecular tumor markers and analyzed their suitability for the detection of circulating tumor DNA in sera of cervical cancer patients...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28936976/progress-in-studies-of-the-mechanisms-and-clinical-diagnosis-of-cervical-carcinoma-associated-with-genomic-integration-of-high-risk-human-papillomavirus-dna
#8
Sha-Sha Huang, Deng-Zai Hao, Yan Zhang, Hou-Ming Liu, Wan-Shui Shan
High-risk human papillomavirus (hrHPV) has been identified as a key factor in the development of cervical cancer. Integration of viral DNA into the host genome has been postulated as an important etiological event during cervical carcinogenesis. High-risk HPV DNA integration frequently results in either the deletion or interruption of the large fragment of E1 and E2 region and the overexpression of oncogenes E6 and E7 in the viral genome, and the activation of oncogenes and the inactivation of tumor suppressors in host genome...
September 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28936208/cas9-nickase-assisted-rna-repression-enables-stable-and-efficient-manipulation-of-essential-metabolic-genes-in-clostridium-cellulolyticum
#9
Tao Xu, Yongchao Li, Zhili He, Joy D Van Nostrand, Jizhong Zhou
Essential gene functions remain largely underexplored in bacteria. Clostridium cellulolyticum is a promising candidate for consolidated bioprocessing; however, its genetic manipulation to reduce the formation of less-valuable acetate is technically challenging due to the essentiality of acetate-producing genes. Here we developed a Cas9 nickase-assisted chromosome-based RNA repression to stably manipulate essential genes in C. cellulolyticum. Our plasmid-based expression of antisense RNA (asRNA) molecules targeting the phosphotransacetylase (pta) gene successfully reduced the enzymatic activity by 35% in cellobiose-grown cells, metabolically decreased the acetate titer by 15 and 52% in wildtype transformants on cellulose and xylan, respectively...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28935963/differentially-expressed-genes-and-canonical-pathways-in-the-ascending-thoracic-aortic-aneurysm-the-tampere-vascular-study
#10
Miska Sulkava, Emma Raitoharju, Ari Mennander, Mari Levula, Ilkka Seppälä, Leo-Pekka Lyytikäinen, Otso Järvinen, Thomas Illig, Norman Klopp, Nina Mononen, Reijo Laaksonen, Mika Kähönen, Niku Oksala, Terho Lehtimäki
Ascending thoracic aortic aneurysm (ATAA) is a multifactorial disease with a strong inflammatory component. Surgery is often required to prevent aortic rupture and dissection. We performed gene expression analysis (Illumina HumanHT-12 version 3 Expression BeadChip) for 32 samples from ATAA (26 without/6 with dissection), and 28 left internal thoracic arteries (controls) collected in Tampere Vascular study. We compared expression profiles and conducted pathway analysis using Ingenuity Pathway Analysis (IPA) to reveal differences between ATAA and a healthy artery wall...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935922/arabidopsis-r1r2r3-myb-proteins-are-essential-for-inhibiting-cell-division-in-response-to-dna-damage
#11
Poyu Chen, Hirotomo Takatsuka, Naoki Takahashi, Rie Kurata, Yoichiro Fukao, Kosuke Kobayashi, Masaki Ito, Masaaki Umeda
Inhibition of cell division is an active response to DNA damage that enables cells to maintain genome integrity. However, how DNA damage arrests the plant cell cycle is largely unknown. Here, we show that the repressor-type R1R2R3-Myb transcription factors (Rep-MYBs), which suppress G2/M-specific genes, are required to inhibit cell division in response to DNA damage. Knockout mutants are resistant to agents that cause DNA double-strand breaks and replication stress. Cyclin-dependent kinases (CDKs) can phosphorylate Rep-MYBs in vitro and are involved in their proteasomal degradation...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28935855/establishing-multiple-omics-baselines-for-three-southeast-asian-populations-in-the-singapore-integrative-omics-study
#12
Woei-Yuh Saw, Erwin Tantoso, Husna Begum, Lihan Zhou, Ruiyang Zou, Cheng He, Sze Ling Chan, Linda Wei-Lin Tan, Lai-Ping Wong, Wenting Xu, Don Kyin Nwe Moong, Yenly Lim, Bowen Li, Nisha Esakimuthu Pillai, Trevor A Peterson, Tomasz Bielawny, Peter J Meikle, Piyushkumar A Mundra, Wei-Yen Lim, Ma Luo, Kee-Seng Chia, Rick Twee-Hee Ong, Liam R Brunham, Chiea-Chuen Khor, Heng Phon Too, Richie Soong, Markus R Wenk, Peter Little, Yik-Ying Teo
The Singapore Integrative Omics Study provides valuable insights on establishing population reference measurement in 364 Chinese, Malay, and Indian individuals. These measurements include > 2.5 millions genetic variants, 21,649 transcripts expression, 282 lipid species quantification, and 284 clinical, lifestyle, and dietary variables. This concept paper introduces the depth of the data resource, and investigates the extent of ethnic variation at these omics and non-omics biomarkers. It is evident that there are specific biomarkers in each of these platforms to differentiate between the ethnicities, and intra-population analyses suggest that Chinese and Indians are the most biologically homogeneous and heterogeneous, respectively, of the three groups...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28934488/de-novo-pathway-based-biomarker-identification
#13
Nicolas Alcaraz, Markus List, Richa Batra, Fabio Vandin, Henrik J Ditzel, Jan Baumbach
Gene expression profiles have been extensively discussed as an aid to guide the therapy by predicting disease outcome for the patients suffering from complex diseases, such as cancer. However, prediction models built upon single-gene (SG) features show poor stability and performance on independent datasets. Attempts to mitigate these drawbacks have led to the development of network-based approaches that integrate pathway information to produce meta-gene (MG) features. Also, MG approaches have only dealt with the two-class problem of good versus poor outcome prediction...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934480/hydroxyl-radical-footprinting-combined-with-molecular-modeling-identifies-unique-features-of-dna-conformation-and-nucleosome-positioning
#14
Alexey K Shaytan, Hua Xiao, Grigoriy A Armeev, Carl Wu, David Landsman, Anna R Panchenko
Nucleosomes are the most abundant protein-DNA complexes in eukaryotes that provide compaction of genomic DNA and are implicated in regulation of transcription, DNA replication and repair. The details of DNA positioning on the nucleosome and the DNA conformation can provide key regulatory signals. Hydroxyl-radical footprinting (HRF) of protein-DNA complexes is a chemical technique that probes nucleosome organization in solution with a high precision unattainable by other methods. In this work we propose an integrative modeling method for constructing high-resolution atomistic models of nucleosomes based on HRF experiments...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934476/crystal-structure-of-an-engineered-hiv-specific-recombinase-for-removal-of-integrated-proviral-dna
#15
Gretchen Meinke, Janet Karpinski, Frank Buchholz, Andrew Bohm
As part of the HIV infection cycle, viral DNA inserts into the genome of host cells such that the integrated DNA encoding the viral proteins is flanked by long terminal repeat (LTR) regions from the retrovirus. In an effort to develop novel genome editing techniques that safely excise HIV provirus from cells, Tre, an engineered version of Cre recombinase, was designed to target a 34-bp sequence within the HIV-1 LTR (loxLTR). The sequence targeted by Tre lacks the symmetry present in loxP, the natural DNA substrate for Cre...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934472/controlled-re-activation-of-epigenetically-silenced-tet-promoter-driven-transgene-expression-by-targeted-demethylation
#16
Natascha Gödecke, Lisha Zha, Shawal Spencer, Sara Behme, Pamela Riemer, Michael Rehli, Hansjörg Hauser, Dagmar Wirth
Faithful expression of transgenes in cell cultures and mice is often challenged by locus dependent epigenetic silencing. We investigated silencing of Tet-controlled expression cassettes within the mouse ROSA26 locus. We observed pronounced DNA methylation of the Tet promoter concomitant with loss of expression in mES cells as well as in differentiated cells and transgenic animals. Strikingly, the ROSA26 promoter remains active and methylation free indicating that this silencing mechanism specifically affects the transgene, but does not spread to the host's chromosomal neighborhood...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934297/molecular-and-biological-characterization-of-%C3%AF-rs551-a-filamentous-bacteriophage-isolated-from-a-race-3-biovar-2-strain-of-ralstonia-solanacearum
#17
Abdelmonim Ali Ahmad, Michael J Stulberg, John Patrick Mershon, Dimitre S Mollov, Qi Huang
A filamentous bacteriophage, designated ϕRs551, was isolated and purified from the quarantine and select agent phytopathogen Ralstonia solanacearum race 3 biovar 2 strain UW551 (phylotype IIB sequevar 1) grown under normal culture conditions. Electron microscopy suggested that ϕRs551 is a member of the family Inoviridae, and is about 1200 nm long and 7 nm wide. ϕRs551 has a genome of 7929 nucleotides containing 14 open reading frames, and is the first isolated virion that contains a resolvase (ORF13) and putative type-2 phage repressor (ORF14)...
2017: PloS One
https://www.readbyqxmd.com/read/28934286/denitrification-potential-of-the-eastern-oyster-microbiome-using-a-16s-rrna-gene-based-metabolic-inference-approach
#18
Ann Arfken, Bongkeun Song, Jeff S Bowman, Michael Piehler
The eastern oyster (Crassostrea virginica) is a foundation species providing significant ecosystem services. However, the roles of oyster microbiomes have not been integrated into any of the services, particularly nitrogen removal through denitrification. We investigated the composition and denitrification potential of oyster microbiomes with an approach that combined 16S rRNA gene analysis, metabolic inference, qPCR of the nitrous oxide reductase gene (nosZ), and N2 flux measurements. Microbiomes of the oyster digestive gland, the oyster shell, and sediments adjacent to the oyster reef were examined based on next generation sequencing (NGS) of 16S rRNA gene amplicons...
2017: PloS One
https://www.readbyqxmd.com/read/28933220/elucidation-of-gene-expression-patterns-in-the-brain-after-spinal-cord-injury
#19
Ahreum Baek, Sung-Rae Cho, Sung Hoon Kim
Spinal cord injury (SCI) is a devastating neurological disease. The pathophysiological mechanisms of SCI have been reported to be relevant to central nervous system injury such as brain injury. In this study, gene expression of the brain after SCI was elucidated using transcriptome analysis to characterize the temporal changes in global gene expression patterns in a SCI mouse model. Subjects were randomly classified into 3 groups: sham control, acute (3 h post-injury), and subacute (2 wk post-injury) groups...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28933072/-metabolomics-research-of-medicinal-plants
#20
Li-Xin Duan, Yun-Tao Dai, Chao Sun, Shi-Lin Chen
Metabolomics is the comprehensively study of chemical processes involving small molecule metabolites. It is an important part of systems biology, and is widely applied in complex traditional Chinese medicine(TCM)system. Metabolites biosynthesized by medicinal plants are the effective basis for TCM. Metabolomics studies of medicinal plants will usher in a new period of vigorous development with the implementation of Herb Genome Program and the development of TCM synthetic biology. This manuscript introduces the recent research progresses of metabolomics technology and the main research contents of metabolomics studies for medicinal plants, including identification and quality evaluation for medicinal plants, cultivars breeding, stress resistance, metabolic pathways, metabolic network, metabolic engineering and synthetic biology researches...
November 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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