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https://www.readbyqxmd.com/read/28440489/genome-wide-dna-methylation-sequencing-reveals-mir-663a-is-a-novel-epimutation-candidate-in-cimp-high-endometrial-cancer
#1
Megumi Yanokura, Kouji Banno, Masataka Adachi, Daisuke Aoki, Kuniya Abe
Aberrant DNA methylation is widely observed in many cancers. Concurrent DNA methylation of multiple genes occurs in endometrial cancer and is referred to as the CpG island methylator phenotype (CIMP). However, the features and causes of CIMP-positive endometrial cancer are not well understood. To investigate DNA methylation features characteristic to CIMP-positive endometrial cancer, we first classified samples from 25 patients with endometrial cancer based on the methylation status of three genes, i.e. MLH1, CDH1 (E-cadherin) and APC: CIMP-high (CIMP-H, 2/25, 8...
April 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28439875/epigenetic-repression-of-mir-375-is-the-dominant-mechanism-for-constitutive-activation-of-the-pdpk1-rps6ka3-signalling-axis-in-multiple-myeloma
#2
Shotaro Tatekawa, Yoshiaki Chinen, Masaki Ri, Tomoko Narita, Yuji Shimura, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Tsutomu Kobayashi, Eri Kawata, Nobuhiko Uoshima, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Handa, Shinsuke Iida, Junya Kuroda
Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28438683/identification-and-expression-of-piwil2-in-turbot-scophthalmus-maximus-with-implications-of-the-involvement-in-embryonic-and-gonadal-development
#3
Huizhen Wang, Bo Wang, Xiaobing Liu, Yuezhong Liu, Xinxin Du, Quanqi Zhang, XuBo Wang
Piwil2, a member of the Argonaute family, is involved in the biogenesis of PIWI-interacting RNAs (piRNAs) and plays an important role in regulating gametogenesis. In the present study, we identified turbot Scophthalmus maximus piwil2 gene, named Smpiwil2, which contained a PAZ domain and a PIWI domain. Sequence comparison, genomic structure and phylogenetic analyses showed that Smpiwil2 is homologous to that of teleosts and tetrapods. The Smpiwil2 transcript showed higher expression in ovary than in testis, demonstrating a sexually dimorphic gene expression pattern...
April 21, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28438527/the-baf-brg1-brm-associated-factor-chromatin-remodeling-complex-exhibits-ethanol-sensitivity-in-fetal-neural-progenitor-cells-and-regulates-transcription-at-the-mir-9-2-encoding-gene-locus
#4
Sasha G Burrowes, Nihal A Salem, Alexander M Tseng, Sridevi Balaraman, Marisa R Pinson, Cadianna Garcia, Rajesh C Miranda
Fetal alcohol spectrum disorders are a leading cause of intellectual disability worldwide. Previous studies have shown that developmental ethanol exposure results in loss of microRNAs (miRNAs), including miR-9, and loss of these miRNAs, in turn, mediates some of ethanol's teratogenic effects in the developing brain. We previously found that ethanol increased methylation at the miR-9-2 encoding gene locus in mouse fetal neural stem cells (NSC), advancing a mechanism for epigenetic silencing of this locus and consequently, miR-9 loss in NSCs...
April 7, 2017: Alcohol
https://www.readbyqxmd.com/read/28432711/vdr-gene-methylation-as-a-molecular-adaption-to-light-exposure-historic-recent-and-genetic-influences
#5
Emma L Beckett, Patrice Jones, Martin Veysey, Konsta Duesing, Charlotte Martin, John Furst, Zoe Yates, Nina G Jablonski, George Chaplin, Mark Lucock
OBJECTIVES: The vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors. We examined whether degree of VDR gene methylation acts as a molecular adaptation to light exposure. We explored this in the context of photoperiod at conception, recent UV irradiance at 305 nm, and gene-latitude effects. METHODS: Eighty subjects were examined for VDR gene-CpG island methylation density. VDR gene variants were also examined by PCR-RFLP. RESULTS: Photoperiod at conception was significantly positively related to VDR methylation density, explaining 17% of the variance in methylation (r(2)  = 0...
April 22, 2017: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/28430929/promoter-polymorphism-rs886205-genotype-interacts-with-dna-methylation-of-the-aldh2-regulatory-region-in-alcohol-dependence
#6
Hansi Pathak, Helge Frieling, Stefan Bleich, Alexander Glahn, Annemarie Heberlein, Mani Haschemi Nassab, Thomas Hillemacher, Alexandra Burkert, Mathias Rhein
Aims: Aldehyde dehydrogenase 2 (ALDH2) protects cells from ethanol toxicity by metabolizing acetaldehyde. We studied the single nucleotide polymorphism (SNP) rs886205s located between a negative and a positive regulating promoter element in the ALDH2 gene. The negative regulatory region was already associated with differential DNA methylation in the two allele variations of rs886205 SNP. Another CpG island, in the positive regulatory region of the ALDH2 promoter, extends through the SNP rs886205 and a nuclear receptor response element...
May 1, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28427182/identification-of-dbccr1-as-a-suppressor-in-the-development-of-lung-cancer-that-is-associated-with-increased-dna-methyltransferase-1
#7
Guoren Zhou, Jinjun Ye, Ying Fang, Zhi Zhang, Jingyuan Zhang, Lei Sun, Jifeng Feng
Accumulating evidence has pointed to a role of the CpG island hypermethylation in the regulation of cancer-related genes in tumor progression. However, the biological impacts in cancer pathogenesis associated with down-regulation of such gene targets remains elusive. Here we focused on a potential target of hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is significantly lower in the lung cancer tissues compared with adjacent non-tumor tissues of patients...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426276/integrative-epigenetic-and-genetic-pan-cancer-somatic-alteration-portraits
#8
Lucas A Salas, Kevin C Johnson, Devin C Koestler, Dylan E O'Sullivan, Brock C Christensen
Genetic and epigenetic alterations are required for carcinogenesis and the mutation burden across tumor types has been investigated. Here, we investigate epigenetic alterations with a novel measure of global DNA methylation dysregulation, the methylation dysregulation index (MDI), across 14 cancer types in The Cancer Genome Atlas (TCGA) database. DNA methylation data-obtained using Illumina HumanMethylation450 BeadChip-was accessed from TCGA. We calculated the MDI in 14 tumor types (n = 5,592 tumors), using adjacent normal tissues (n = 701) from each tumor site...
April 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28422997/promoter-hypermethylation-as-a-mechanism-for-lamin-a-c-silencing-in-a-subset-of-neuroblastoma-cells
#9
Ines Rauschert, Fabian Aldunate, Jens Preussner, Miguel Arocena-Sutz, Vanina Peraza, Mario Looso, Juan C Benech, Ruben Agrelo
Nuclear lamins support the nuclear envelope and provide anchorage sites for chromatin. They are involved in DNA synthesis, transcription, and replication. It has previously been reported that the lack of Lamin A/C expression in lymphoma and leukaemia is due to CpG island promoter hypermethylation. Here, we provide evidence that Lamin A/C is silenced via this mechanism in a subset of neuroblastoma cells. Moreover, Lamin A/C expression can be restored with a demethylating agent. Importantly, Lamin A/C reintroduction reduced cell growth kinetics and impaired migration, invasion, and anchorage-independent cell growth...
2017: PloS One
https://www.readbyqxmd.com/read/28422723/serrated-adenocarcinoma-morphology-in-colorectal-mucinous-adenocarcinoma-is-associated-with-improved-patient-survival
#10
Chung-Ta Lee, Yu-Chuan Huang, Liang-Yi Hung, Nan-Haw Chow, Pei-Fang Su, Chung-Liang Ho, Hung-Wen Tsai, Yi-Lin Chen, Shao-Chieh Lin, Bo-Wen Lin, Peng-Chan Lin, Jenq-Chang Lee
Colorectal mucinous adenocarcinoma (MAC) and serrated adenocarcinoma (SAC) share many characteristics, including right-side colon location, frequent mucin production, and various molecular features. This study examined the frequency of SAC morphology in MACs. We assessed the correlation of SAC morphology with clinicopathological parameters, molecular characteristics, and patient prognosis. Eighty-eight colorectal MACs were collected and reviewed for SAC morphology according to Makinen's criteria. We sequenced KRAS and BRAF, assessed CpG island methylator phenotype (CIMP) frequency, and analyzed DNA mismatch repair enzyme levels using immunohistochemistry in tumor samples...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419930/design-synthesis-and-anticancer-potential-of-nsc-319745-hydroxamic-acid-derivatives-as-dnmt-and-hdac-inhibitors
#11
Zigao Yuan, Qinsheng Sun, Dan Li, Shuangshuang Miao, Shaopeng Chen, Lu Song, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important epigenetic targets during anticancer drug development. Recent study indicates that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain cancers, therefore, development of molecules targeting both DNMT and HDAC is of therapeutic advantage against these cancers. Based on the structure of DNMT inhibitor NSC-319745 and the pharmacophore characteristics of HDAC inhibitors, a series of hydroxamic acid derivatives of NSC-319745 were designed and synthesized as DNMT and HDAC multifunctional inhibitors...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28418032/a-new-approach-to-evaluating-aberrant-dna-methylation-profiles-in-hepatocellular-carcinoma-as-potential-biomarkers
#12
Yuan Yang, Linghao Zhao, Bo Huang, Guojun Hou, Beibei Zhou, Jin Qian, Shengxian Yuan, Huasheng Xiao, Minghui Li, Weiping Zhou
Hypermethylation of CpG islands in the promoter region of tumor suppressor genes (TSGs) and their subsequent silencing is thought to be one of the main mechanisms of carcinogenesis. MBD2b enrichment coupled with a NimbleGen array was applied to examine the genome-wide CpG island methylation profile of hepatocellular carcinoma (HCC). Hypermethylated DNA of 58 pairs of HCC and adjacent tissue samples was enriched and hybridized in the same array. Aberrant hypermethylated peaks of HCC and adjacent tissues were screened and annotated after data processing using NimbleScan2...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416947/dna-methylation-profiles-of-blood-cells-are-distinct-between-early-onset-obese-and-control-individuals
#13
Je-Keun Rhee, Jin-Hee Lee, Hae Kyung Yang, Tae-Min Kim, Kun-Ho Yoon
Obesity is a highly prevalent, chronic disorder that has been increasing in incidence in young patients. Both epigenetic and genetic aberrations may play a role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic analyses will advance our understanding of the detailed molecular mechanisms underlying obesity and aid in the selection of potential biomarkers for obesity in youth. Here, we performed microarray-based DNA methylation and gene expression profiling of peripheral white blood cells obtained from six young, obese individuals and six healthy controls...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28416772/dna-methylation-of-mettl7a-gene-body-regulates-its-transcriptional-level-in-thyroid-cancer
#14
Shasha Zhou, Yihang Shen, Min Zheng, Linlin Wang, Raymond Che, Wanning Hu, Pin Li
DNA methylation is the best-studied epigenetic mechanism for regulating gene transcription and maintaining genome stability. Current research progress of transcriptional regulation by DNA methylation mostly focuses on promoter region where hypomethylated CpG islands are present transcriptional activity, as hypermethylated CpG islands generally result in gene repression. Recently, the DNA methylation patterns across the gene body (intragenic methylation) have increasingly attracted attention towards their role in transcriptional regulation and efficiency, due to the improvement of numerous genome-wide DNA methylation profiling studies...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416650/epigenetic-regulator-cxxc5-recruits-dna-demethylase-tet2-to-regulate-tlr7-9-elicited-ifn-response-in-pdcs
#15
Shixin Ma, Xiaoling Wan, Zihou Deng, Lei Shi, Congfang Hao, Zhenyuan Zhou, Chun Zhou, Yiyuan Fang, Jinghua Liu, Jing Yang, Xia Chen, Tiantian Li, Aiping Zang, Shigang Yin, Bin Li, Joel Plumas, Laurence Chaperot, Xiaoming Zhang, Guoliang Xu, Lubin Jiang, Nan Shen, Sidong Xiong, Xiaoming Gao, Yan Zhang, Hui Xiao
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs...
April 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28415780/long-noncoding-rna-pcat-14-induces-proliferation-and-invasion-by-hepatocellular-carcinoma-cells-by-inducing-methylation-of-mir-372
#16
Yawei Wang, Ye Hu, Gang Wu, Ye Yang, Yanqing Tang, Wanchuan Zhang, Kaiyu Wang, Yu Liu, Xin Wang, Tiemin Li
Long non-coding RNAs (lncRNAs) regulate oncogenesis by inducing methylation of CpG islands to silence target genes. Here we show that the lncRNA PCAT-14 is overexpressed in patients with hepatocellular carcinoma (HCC), and is associated with a poor prognosis after surgery. Our results demonstrate that PCAT-14 promotes proliferation, invasion, and cell cycle arrest in HCC cells. In addition, PCAT-14 inhibits miR-372 expression by inducing methylation of the miR-372 promoter. Simultaneously, miR-372 eliminates the effects of PCAT-14 on proliferation, invasion, and cell cycle in HCC cells...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415743/survival-differences-of-cimp-subtypes-integrated-with-cna-information-in-human-breast-cancer
#17
Huihan Wang, Weili Yan, Shumei Zhang, Yue Gu, Yihan Wang, Yanjun Wei, Hongbo Liu, Fang Wang, Qiong Wu, Yan Zhang
CpG island methylator phenotype of breast cancer is associated with widespread aberrant methylation at specified CpG islands and distinct patient outcomes. However, the influence of copy number contributing to the prognosis of tumors with different CpG island methylator phenotypes is still unclear. We analyzed both genetic (copy number) and epigenetic alterations in 765 breast cancers from The Cancer Genome Atlas data portal and got a panel of 15 biomarkers for copy number and methylation status evaluation...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414811/tissue-expression-profiles-and-transcriptional-regulation-of-elongase-of-very-long-chain-fatty-acid-6-in-bovine-mammary-epithelial-cells
#18
Si Chen, Hua He, Xiaolin Liu
In mammals, very long chain fatty acids (VLCFAs) perform pleiotropic roles in a wide range of biological processes, such as cell membrane formation, cell signal transduction, and endocrine regulation. Beef and milk are abundant of palmitic acid which can be further elongated into stearic acid for synthesizing VLCFAs. Elongase of very long chain fatty acid 6 (ELOVL6) is a rate-limiting enzyme for converting palmitic acid to stearic acid. Consequently, investigating the tissue expression patterns and transcriptional regulation of bovine ELOVL6 can provide new insights into improving the composition of beneficial fats in cattle and expanding the knowledge of transcriptional regulation mechanism among domestic animals...
2017: PloS One
https://www.readbyqxmd.com/read/28413449/links-between-dna-methylation-and-nucleosome-occupancy-in-the-human-genome
#19
Clayton K Collings, John N Anderson
BACKGROUND: DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation levels of DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while other studies have shown that the nucleosome core is the preferred site of methylation. In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28409176/systemic-analysis-of-osteoblast-specific-dna-methylation-marks-reveals-novel-epigenetic-basis-of-osteoblast-differentiation
#20
Fangtang Yu, Hui Shen, Hong-Wen Deng
DNA methylation is an important epigenetic modification that contributes to the lineage commitment and specific functions of different cell types. In this study, we compared ENCODE-generated genome-wide DNA methylation profiles of human osteoblast with 21 other types of human cells in order to identify osteoblast-specific methylation events. For most of the cell strains, data from two isogenic replicates were included, resulting in a total of 51 DNA methylation datasets. We identified 852 significant osteoblast-specific differentially methylated CpGs (DMCs) and 295 significant differentially methylated regions (DMRs)...
June 2017: Bone Reports
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