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Yang Liu, Rongyao Huang, Yu Liu, Wanlu Song, Yuting Wang, Yang Yang, Shengcheng Dong, Xuerui Yang
Although the DNA methylome profiles have been available in large cancer cohorts such as The Cancer Genome Atlas (TCGA), integrative analysis of the DNA methylome architectures in a pan-cancer manner is still limited. In the present study, we aimed to systematically dissect the insightful features related to the inter-tumoral DNA methylome heterogeneity in a pan-cancer context of 21 cancers in TCGA. First, pan-cancer clustering of the DNA methylomes revealed convergence of cancers and, meanwhile, new classifications of cancer subtypes, which are often associated to prognostic differences...
August 19, 2018: International Journal of Cancer. Journal International du Cancer
Ovidiu Paun, Koen J F Verhoeven, Christina L Richards
I. II. III. IV. V. VI. SUMMARY: Investigating the features and implications of epigenetic mechanisms across the breadth of organisms and ecosystems is important for understanding the ecological relevance of epigenetics. Several cost-effective reduced representation bisulfite sequencing approaches (RRBS) have been recently developed and applied to different organisms that lack a well annotated reference genome. These new approaches improve the assessment of epigenetic diversity in ecological settings and may provide functional insights...
August 19, 2018: New Phytologist
Marco Tulio Mendes Ferreira, Laiane Corsini Rocha, Matheus Braga Zanon Vitoriano, Andréa Mittelmann, Vânia Helena Techio
The grasses of the Lolium-Festuca complex show a prominent role in world agricultural scenario. Several studies have demonstrated that the plasticity of 45S rDNA sites has been recently associated with the possible fragility of the loci. Often, these fragile sites were observed as extended sites and gaps in metaphases. This organization can be evaluated in relation to their transcriptional activity/accessibility through epigenetic changes. Thus, this study aimed to investigate the relationship of the 5-methylcytosine and histone H3 lysine-9 dimethylation in different conformations of 45S rDNA sites in interphase nuclei and in metaphase chromosomes of L...
August 18, 2018: Molecular Biology Reports
Charleen D Adams
The epidemiologic study of DNA methylation (DNAm) and mental health is a burgeoning area, but confounding and reverse causation remain important to know about. Whether use of non-brain tissues is appropriate when investigating brain phenotypes depends on the hypothesis and whether the goal is causality or to identify biomarkers. Look-ups of the correspondence between DNAm in blood and brain and use of Mendelian randomization (MR) can be done to follow-up, to some degree, on the causal nature of some findings...
August 9, 2018: Current Opinion in Psychology
Naoya Miyashita, Masafumi Horie, Hiroshi I Suzuki, Masahito Yoshihara, Dijana Djureinovic, Johan Persson, Hans Brunnström, Cecilia Lindskog, Hedvig Elfving, Patrick Micke, Akira Saito, Takahide Nagase
A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete-scute complex homolog 1 (ASCL1), common to high-grade neuroendocrine tumors, small cell lung cancer and large cell neuroendocrine carcinoma. The aim of this study was to characterize clinical and molecular features of ASCL1-positive lung adenocarcinoma by utilizing recent transcriptome profiling in multiple patient cohorts and genome-wide epigenetic profiling including data from The Cancer Genome Atlas (TCGA). The ASCL1-positive subtype of lung adenocarcinoma developed preferentially in current or former smokers and usually did not harbor epidermal growth factor receptor (EGFR) mutations...
August 16, 2018: Journal of Thoracic Oncology
Xiong Liu, Chun Li, Rengdong Zhang, Wenjun Xiao, Xia Niu, Xiajun Ye, Zijia Li, Yuxian Guo, Junyu Tan, Yaochen Li
It is well known that epithelial-mesenchymal transition (EMT) can confer cancer cells with invasive and migratory capabilities associated with distant metastasis. As a key upstream factor in the Hippo pathway, Kibra (wwc1 gene) has been shown to suppress EMT in breast cancer cells, and we have found that its expression is reduced or lost completely in both human breast cancer cell lines and clinical tissue samples, particularly in triple negative breast cancer (TNBC). Unfortunately, the molecular mechanisms underlying this progression-associated event remain to be elucidated...
August 16, 2018: Cellular Signalling
Saliha Esenboga, Can Akal, Betül Karaatmaca, Baran Erman, Sibel Dogan, Diclehan Orhan, Kaan Boztug, Deniz Ayvaz, İlhan Tezcan
V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections...
August 16, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Martin Sidler, Karen J Aitken, Jia-Xin Jiang, Chris Sotiropoulos, Prateek Aggarwal, Arsalan Anees, Cynthia Chong, Aliza Siebenaller, Thenuka Thanabalasingam, J Maxwell White, Sanaa Choufani, Rosanna Weksberg, Bruno Sangiorgi, Jeff Wrana, Paul Delgado-Olguin, Darius J Bägli
Chronic bladder obstruction and bladder smooth muscle cell (BSMC) stretch provide fibrotic and mechanical environments that can induce epigenetic change. Therefore, we examined the role of DNA methylation in bladder pathology and transcriptional control. Sprague-Dawley female rats underwent partial bladder obstruction by ligation of a silk suture around the proximal urethra next to a 0.9 mm steel rod. Sham operation comprised passing the suture around the urethra. After two weeks, rats were randomized to normal saline or DNA methyltransferase inhibitor, 5-aza-2-deoxycytidine (DAC) at 1 mg/kg, 3 times/week intraperitoneally...
August 16, 2018: American Journal of Pathology
Viktoria Johansson, Christina M Hultman, Isabelle Kizling, Lennart Martinsson, Jacqueline Borg, Anna Hedman, Tyrone D Cannon
The schizophrenia and bipolar twin study in Sweden (STAR) is a large nation-wide cohort of monozygotic (MZ) and dizygotic (DZ) same-sex twins with schizophrenia or bipolar disorder and healthy control pairs, extensively characterized with brain imaging, neuropsychological tests, biomarkers, genetic testing, psychiatric symptoms and personality traits. The purpose is to investigate genetic and environmental mechanisms that give rise to schizophrenia and bipolar disorder as well as the intermediate phenotypes...
August 15, 2018: Schizophrenia Research
Balabhadrapatruni V S K Chakravarthi, Maria Del Carmen Rodriguez Pena, Sumit Agarwal, Darshan S Chandrashekar, Sai Akshaya Hodigere Balasubramanya, Fayez J Jabboure, Andres Matoso, Trinity J Bivalacqua, Katayoon Rezaei, Alcides Chaux, William E Grizzle, Guru Sonpavde, Jennifer Gordetsky, George J Netto, Sooryanarayana Varambally
Genomic and transcriptome sequencing of bladder cancer (BLCA) has identified multiple molecular alterations during cancer progression. Many of these identified genetic and epigenetic changes play a role in the progression of this disease. Studies have identified molecular subtypes in muscle-invasive bladder cancer (MIBC) with different sensitivities to frontline therapy suggesting the heterogeneity in these tumors and the importance of molecular characterization of MIBC to provide effective treatment. Specifically, it has become increasingly evident, as demonstrated by The Cancer Genome Atlas project, that metabolic enzymes are commonly dysregulated in BLCA...
August 14, 2018: Neoplasia: An International Journal for Oncology Research
Aishwarya Kakade, Baby Kumari, Pankaj Singh Dholaniya
Parkinson's Disease (PD) is described as a progressive neurological disorder caused by the degeneration of dopaminergic neurons in substantia nigra pars compacta. The pathogenesis of the disease is not fully understood but it has been linked with complex genetic, epigenetic and environmental interactions. A substantial number of studies have shown the role of epigenetic modifications in support of the progression of PD. In the present study, we have analyzed the data containing methylation patterns of 1726 transcripts captured over from 66 samples of 450k, which includes 43 controls and 23 diseased samples...
August 15, 2018: Journal of Theoretical Biology
Ya-Sian Chang, Chun-Chi Chang, Hsi-Yuan Huang, Chien-Yu Lin, Kun-Tu Yeh, Jan-Gowth Chang
Genetic and epigenetic alterations are associated with the progression and prognosis of medullary thyroid carcinoma (MTC). We performed whole-exome sequencing of tumor tissue from seven patients with sporadic MTC using an Illumina HiSeq 2000 sequencing system. We conducted Sanger sequencing to confirm the somatic mutations in both tumor and matched normal tissues. We applied Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis with the Database for Annotation, Visualization, and Integrated Discovery and STRING for pathway analysis...
August 17, 2018: Endocrine Pathology
Chika Miyagi-Shiohira, Yoshiki Nakashima, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. Furthermore, our recent study demonstrated the generation of induced tissue-specific stem (iTS) cells by transient overexpression of the reprogramming factors using a plasmid combined with tissue-specific selection. In this study, we were able to generate RNA-based iTS cells that utilize a single, synthetic, self-replicating VEE-RF RNA replicon expressing four reprogramming factors (OCT4, KLF4, SOX2, and GLIS1)...
August 17, 2018: Scientific Reports
Yanrui Jiang, Makiko Seimiya, Tommy Beat Schlumpf, Renato Paro
Polycomb group proteins are epigenetic regulators maintaining transcriptional memory during cellular proliferation. In Drosophila larvae, malfunction of Polyhomeotic (Ph), a member of the PRC1 silencing complex, results in neoplastic growth. Here, we report an intrinsic tumour suppression mechanism mediated by the steroid hormone ecdysone during metamorphosis. Ecdysone alters neoplastic growth into a nontumorigenic state of the mutant ph cells which then become eliminated during adult stage. We demonstrate that ecdysone exerts this function by inducing a heterochronic network encompassing the activation of the microRNA lethal-7, which suppresses its target gene chronologically inappropriate morphogenesis...
August 17, 2018: Nature Communications
David Martino, Melanie Neeland, Thanh Dang, Joanna Cobb, Justine Ellis, Alice Barnett, Mimi Tang, Peter Vuillermin, Katrina Allen, Richard Saffery
Food allergy poses a significant clinical and public health burden affecting 2-10% of infants. Using integrated DNA methylation and transcriptomic profiling, we found that polyclonal activation of naive CD4+ T cells through the T cell receptor results in poorer lymphoproliferative responses in children with immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle-related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory genes (IL1R, IL18RAP, CD82) underpins this suboptimal response...
August 17, 2018: Nature Communications
Wenfei Gu, Enfeng Zhang, Lijun Song, Laiyong Tu, Zhenbin Wang, Feng Tian, Kahaer Aikenmu, Ge Chu, Jiang Zhao
Osteosarcoma is the most common primary malignant bone tumor and long non-coding RNAs (lncRNAs) have been proved to epigenetically regulate the oncogenesis of osteosarcoma. In this research, we investigate the role of lncRNA HOXD-AS1 on the osteosarcoma oncogenesis. Results revealed that HOXD-AS1 expression level was significantly up-regulated in osteosarcoma tissue and cells, moreover, the aberrant overexpression predicted the poor prognosis of osteosarcoma patients. Loss-of-functional experiments indicated that HOXD-AS1 silencing inhibited the osteosarcoma cells proliferation and induced G1/G0 phase arrest in vitro, and repressed tumor cell growth in vivo...
July 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Erfei Chen, Qiqi Li, Hua Wang, Fangfang Yang, Lulu Min, Jin Yang
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Accumulation of varieties of epigenetic changes, including miRNA regulation, is one of the fundamental processes driving CRC initiation and progression. Mir-92a has been reported in several studies as an oncogene, and particularly in colorectal cancer, it has become a useful biomarker for early detection of CRC in both serum or stool. The Cancer Genome Atlas (TCGA) is a powerful database to analyze cancer-related genes and their correlation with patients' pathological information...
July 23, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yong Zhang, Sanxiu Huang, Yu Guo, Lingfeng Li
BACKGROUND: Dysregulation of miRNAs is critical for chemosensitivity to platinum-based agents in ovarian cancer (OC) which is the most aggressive gynecological cancer. However, the underlying mechanisms of miRNA-regulated platinum resistance in ovarian cancer remain unclear. In this study, we intended to investigate the effect of miR-1294 on platinum-resistant OC. METHODS: The expression of miR-1294 in OC tissues (n = 30) and cell lines was measured by qRT-PCR...
July 23, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Erfei Chen, Qiqi Li, Hua Wang, Pan Zhang, Xiaojuan Zhao, Fangfang Yang, Jin Yang
MiRNA regulation is a crucial way of epigenetic changes. Mir-32 has been reported in several studies as an oncogene, however, its role and target in colorectal cancer (CRC) remains unclear. In this study, we aimed to explore the role of miR-32 in CRC using bioinformatic analysis and functional assays. We collected 28 pairs of CRC tumor tissues and adjacent normal tissues and confirmed miR-32 was significantly upregulated in CRC. Expression and clinical data from The Cancer Genome Atlas (TCGA) identified miR-32 expression is associated with CRC lymphatic invasion, metastasis, and correlates with patients' poor survival...
July 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Richard C Crist, Benjamin C Reiner, Wade H Berrettini
Opioid use disorder (OUD) affects millions of people worldwide and the risk of developing the disorder has a significant genetic component according to twin and family studies. Identification of the genetic variants underlying this inherited risk has focused on two different methods: candidate gene studies and genome-wide association studies (GWAS). The most studied candidate genes have included the mu-opioid receptor (OPRM1), the delta-opioid receptor (OPRD1), the dopamine D2 receptor (DRD2), and brain-derived neurotrophic factor (BDNF)...
August 9, 2018: Current Opinion in Psychology
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