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Demethylation

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https://www.readbyqxmd.com/read/29331774/the-synergy-of-vitamin-c-with-decitabine-activates-tet2-in-leukemic-cells-and-significantly-improves-overall-survival-in-elderly-patients-with-acute-myeloid-leukemia
#1
Huihui Zhao, Huayuan Zhu, Jiayu Huang, Yu Zhu, Ming Hong, Han Zhu, Jingjing Zhang, Shan Li, Lijia Yang, Yun Lian, Shuai Wang, Jianping Mao, Yaoyu Chen, Jianyong Li, Sixuan Qian
BACKGROUND: Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation at the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic. METHODS: The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29331685/nucleic-adaptability-of-heterokaryons-to-fungicides-in-a-multinucleate-fungus-sclerotinia-homoeocarpa
#2
Dylan Kessler, Hyunkyu Sang, Amanda Bousquet, Jonathan P Hulvey, Dawlyn Garcia, Siyeon Rhee, Yoichiro Hoshino, Toshihiko Yamada, Geunhwa Jung
Sclerotinia homoeocarpa is the causal organism of dollar spot in turfgrasses and is a multinucleate fungus with a history of resistance to multiple fungicide classes. Heterokaryosis gives rise to the coexistence of genetically distinct nuclei within a cell, which contributes to genotypic and phenotypic plasticity in multinucleate fungi. We demonstrate that field isolates, resistant to either a demethylation inhibitor or methyl benzimidazole carbamate fungicide, can form heterokaryons with resistance to each fungicide and adaptability to serial combinations of different fungicide concentrations...
January 10, 2018: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29330295/epigenetic-reprogramming-of-pericentromeric-satellite-dna-in-premalignant-and-malignant-lesions
#3
Nadine H Brueckmann, Christina B Pedersen, Henrik J Ditzel, Morten F Gjerstorff
Repression of repetitive DNA is important for maintaining genomic stability, but is often perturbed in cancer. For instance, the megabase satellite domain at chromosome 1q12 is a common site of genetic rearrangements, such as translocations and deletions. Polycomb-group (PcG) proteins can be observed as large subnuclear domains called polycomb bodies, the composition and cellular function of which has remained elusive. This study, demonstrates that polycomb bodies are canonical subunits of the multiprotein polycomb repressive complex 1 (PRC1) deposited on 1q12 pericentromeric satellite DNA, which are normally maintained as constitutive heterochromatin by other mechanisms...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330146/demethylation-induced-overexpression-of-shc3-drives-c-raf-independent-activation-of-mek-erk-in-hcc
#4
Yun Liu, Xinran Zhang, Baicai Yang, Hao Zhuang, Hua Guo, Wen Wei, Yuan Li, Ruibing Chen, Yongmei Li, Ning Zhang
Invasion and intrahepatic metastasis are major factors of poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we show that increased Src homolog and collagen homolog 3 (Shc3) expression in malignant HCC cell lines associate with HCC invasion and metastasis. Shc3 was significantly upregulated in tumors of 33 HCC patient samples as compared to adjacent normal tissues. Further analysis of 52 HCC patient samples showed that Shc3 expression correlated with microvascular invasion, cancer staging, and poor prognosis...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29329300/symmetric-dimeric-bisbenzimidazoles-dbp-n-reduce-methylation-of-rarb-and-pten-while-significantly-increase-methylation-of-rrna-genes-in-mcf-7-cancer-cells
#5
Svetlana V Kostyuk, Margarita A Kvasha, Daria A Khrabrova, Olga V Kirsanova, Elizaveta S Ershova, Elena M Malinovskaya, Natalia N Veiko, Alexander A Ivanov, Vasiliy S Koval, Alexei L Zhuze, Vadim H Tashlitsky, Pavel E Umriukhin, Sergey I Kutsev, Elizaveta S Gromova
BACKGROUND: Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n) are able to block DNA methyltransferase activities. It was also found that DBP(n) produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome...
2018: PloS One
https://www.readbyqxmd.com/read/29327072/naproxen-is-transformed-via-acetogenesis-and-syntrophic-acetate-oxidation-by-a-methanogenic-wastewater-consortium
#6
Sarah J Wolfson, Abigail W Porter, Julia K Campbell, Lily Y Young
Over-the-counter pharmaceutical compounds can serve as microbial substrates in wastewater treatment processes as well as in the environment. The metabolic pathways and intermediates produced during their degradation, however, are poorly understood. In this study, we investigate an anaerobic wastewater community that metabolizes naproxen via demethylation. Enriched cultures, established from anaerobic digester inocula receiving naproxen as the sole carbon source, transformed naproxen to 6-O-desmethylnaproxen (DMN) within 22 days...
January 11, 2018: Microbial Ecology
https://www.readbyqxmd.com/read/29326345/microrna-452-exerts-growth-suppressive-activity-against-t-cell-acute-lymphoblastic-leukemia
#7
Haihao Wang, Qiannan Guo, Guizhi Zhu, Shuo Zhu, Peiwen Yang, Mingsheng Zhang
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer. Although microRNA (miR)-452 serves as a tumor suppressor in multiple solid tumors, its expression and function in hematological cancers including T-ALL is largely unknown. We measured the expression of miR-452 in 38 T-ALL and 22 normal lymph node samples by real-time PCR analysis. The methylation levels in the promoter of miR-452 were determined using MethyLight assay. The effects of miR-452 overexpression on proliferation, cell cycle distribution, and tumorigenesis were explored...
January 10, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29326044/escherichia-coli-single-stranded-dna-binding-protein-ssb-promotes-alkb-mediated-dna-dealkylation-repair
#8
Richa Nigam, Roy Anindya
Repair of alkylation damage in DNA is essential for maintaining genome integrity. Escherichia coli (E.coli) protein AlkB removes various alkyl DNA adducts including N1-methyladenine (N1meA) and N3-methylcytosine (N3meC) by oxidative demethylation. Previous studies showed that AlkB preferentially removes N1meA and N3meC from single-stranded DNA (ssDNA). It can also remove N1meA and N3meC from double-stranded DNA by base-flipping. Notably, ssDNA produced during DNA replication and recombination, remains bound to E...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29324315/histone-demethylase-kdm5a-inhibits-glioma-cells-migration-and-invasion-by-down-regulating-zeb1
#9
Bin Dai, Hui Huang, Feng Guan, Guangtong Zhu, Zhiyong Xiao, Beibei Mao, Haiyang Su, Zhiqiang Hu
Malignant gliomas are highly lethal cancers worldwide as tumor cells infiltrate to healthy brain tissue invariably. Histone demethylase KDM5A as an oncogene or tumor suppressor in cancer still has been controversial. KDM5A may have a different function in different type cancer cells. However, the specific roles of KDM5A in the progression of glioma remain undiscovered. In this study, we found that compared with primary glioma, metastasis glioma had low KDM5A levels. Besides, lower KDM5A levels were linked to poor survival in glioma cancer patients, indicating that KDM5A is a new prognostic marker for glioma cancer...
January 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29323165/biotransformation-and-tissue-distribution-of-protopine-and-allocryptopine-and-effects-of-plume-poppy-total-alkaloid-on-liver-drug-metabolizing-enzymes
#10
Ya-Jun Huang, Pi Cheng, Zhuo-Yi Zhang, Shi-Jie Tian, Zhi-Liang Sun, Jian-Guo Zeng, Zhao-Ying Liu
In this study, the biotransformation in the plasma, urine and feces of rats following oral administration of protopine (PRO) and allocryptopine (ALL)were explored using HPLC-QqTOF MS. An HPLC-MS/MS method for the determination of tissues was developed and applied to the tissue distribution study in rats following intragastric administration of Plume Poppy Total Alkaloid for 3 weeks. A total of ten PRO metabolites and ten ALL metabolites were characterized in rats in vivo. Among these metabolites, six PRO metabolites and five ALL metabolites were reported for the first time...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320940/methylation-mediated-loss-of-sfrp2-enhances-invasiveness-of-non-small-cell-lung-cancer-cells
#11
X Zhang, X Rong, Y Chen, L Su
The malignancy of non-small cell lung cancer (NSCLC) largely results from its invasive manner. Secreted frizzled-related proteins (SFRPs) have been recently found to suppress the invasiveness of some cancers. On the other hand, the methylation of SFRPs increases protein degradation to reduce the activity of SFRPs, resulting in increased tumor cell invasion and cancer metastasis. However, the role of SFRPs in the invasion of NSCLC has not been reported. Here we analyzed the regulation of SFRPs in NSCLC cells and its effects on cell invasion...
February 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29320849/a-dft-study-on-the-demethylation-reaction-between-methylamine-dimethylamine-trimethylamine-and-tamoxifen-catalyzed-by-a-fe-iv-oxo-porphyrin-complex
#12
Nerea Alberro, Miquel Torrent-Sucarrat, Ana Arrieta, Gloria Rubiales, Fernando P Cossio
In this work, we have studied computationally the N-demethylation reaction of methylamine, dimethylamine and trimethylamine as archetypal examples of primary, secondary and tertiary amines catalyzed by high field low spin Fe-containing enzymes such as cytochromes P450. Using DFT calculations, we have obtained that the expected C-H hydroxylation process is achieved for trimethylamine. When dimethylamine and methylamine were studied, two different reaction mechanisms (C-H hydroxylation and a double hydrogen atom transfer) were computed to be energetically accessible and both are equally preferred...
January 11, 2018: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29319811/identification-of-a-consensus-motif-in-erg28p-required-for-c-4-demethylation-in-yeast-ergosterol-biosynthesis-based-on-mutation-analysis
#13
Xia Ke, Xiao-Yuan Xia, Ren-Chao Zheng, Yu-Guo Zheng
The Erg28p protein is localized to the endoplasmic reticulum (ER), where it acts as a scaffold to tether the C-4 demethylase complex involved in the sterol biosynthesis pathway of Saccharomyces cerevisiae. However, due to the challenges involved in characterizing the interactions of membrane proteins, the precise region of Erg28p that is responsible for the assembly of this enzyme complex remains unknown. To address this question, mutants with serial truncations in the C-terminus of Erg28p were constructed based on a topology prediction of its transmembrane domain...
January 8, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29318692/promoter-hypermethylation-inactivate-tumour-suppressor-fam134b-and-is-associated-with-poor-prognosis-in-colorectal-cancer
#14
Farhadul Islam, Vinod Gopalan, Suja Pillai, Cu-Tai Lu, Kais Kasem, Alfred King-Yin Lam
The present study aims to examine promoter methylation status of FAM134B in a large cohort of patients with colorectal adenocarcinomas. The clinical significances and correlations of FAM134B promoter methylation with its expression are also analysed. Methylation-specific high-resolution melt-curve analysis followed by sequencing was used to identify FAM134B promoter methylation in colorectal adenomas (n=32), colorectal adenocarcinomas (n=164), matched adjacent non-neoplastic colorectal mucosae (n=83) and colon cancer cell lines (n=4)...
January 10, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29318497/epigenetic-mechanism-of-survivin-dysregulation-in-human-cancer
#15
REVIEW
Hui Lyu, Jingcao Huang, Zhimin He, Bolin Liu
Survivin (coding gene BIRC5) is a dual functional protein acting as a critical inhibitor of apoptosis (IAP) and key regulator of cell cycle progression. It is usually produced in embryonic tissues during development and undetectable in most adult tissues. Overexpression of Survivin frequently occurs in various human cancers and increased Survivin correlates with poor clinic outcome, tumor recurrence, and therapeutic resistance. Because of its selective expression in tumor, but not normal tissues, Survivin has been recognized as an attractive target for cancer treatment...
January 4, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29318382/mir-29-silencing-modulates-the-expression-of-target-genes-related-to-proliferation-apoptosis-and-methylation-in-burkitt-lymphoma-cells
#16
Luciano Mazzoccoli, Marcela Cristina Robaina, Alexandre Gustavo Apa, Martin Bonamino, Luciana Wernersbach Pinto, Eduardo Queiroga, Carlos E Bacchi, Claudete Esteves Klumb
PURPOSE: Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis. METHODS: Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression...
January 9, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29317619/phf8-histone-demethylase-deficiency-causes-cognitive-impairments-through-the-mtor-pathway
#17
Xuemei Chen, Shuai Wang, Ying Zhou, Yanfei Han, Shengtian Li, Qing Xu, Longyong Xu, Ziqi Zhu, Youming Deng, Lu Yu, Lulu Song, Adele Pin Chen, Juan Song, Eiki Takahashi, Guang He, Lin He, Weidong Li, Charlie Degui Chen
Epigenomic abnormalities caused by genetic mutation in epigenetic regulators can result in neurodevelopmental disorders, deficiency in neural plasticity and mental retardation. As a histone demethylase, plant homeodomain finger protein 8 (Phf8) is a candidate gene for syndromal and non-specific forms of X-chromosome-linked intellectual disability (XLID). Here we report that Phf8 knockout mice displayed impaired learning and memory, and impaired hippocampal long-term potentiation (LTP) without gross morphological defects...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29317521/ca2-dependent-demethylation-of-phosphatase-pp2ac-promotes-glucose-deprivation-induced-cell-death-independently-of-inhibiting-glycolysis
#18
Ha Yin Lee, Yoko Itahana, Stefan Schuechner, Masahiro Fukuda, H Shawn Je, Egon Ogris, David M Virshup, Koji Itahana
Cancer cells increase glucose metabolism to support aerobic glycolysis. However, only some cancer cells are acutely sensitive to glucose withdrawal, and the underlying mechanism of this selective sensitivity is unclear. We showed that glucose deprivation initiates a cell death pathway in cancer cells that is dependent on the kinase RIPK1. Glucose withdrawal triggered rapid plasma membrane depolarization and an influx of extracellular calcium into the cell through the L-type calcium channel Cav1.3 (CACNA1D), followed by activation of the kinase CAMK1...
January 9, 2018: Science Signaling
https://www.readbyqxmd.com/read/29316399/enrichment-and-quantitative-determination-of-5-hydroxymethyl-2-deoxycytidine-5-formyl-2-deoxycytidine-and-5-carboxyl-2-deoxycytidine-in-human-urine-of-breast-cancer-by-magnetic-high-cross-linked-microporous-polymers-based-on-poly-ionic-liquid
#19
Mengzhe Guo, Liyan Zhang, Yan Du, Wencheng Du, Dantong Liu, Cheng Guo, Yuanjiang Pan, Dao-Quan Tang
5-(hydroxymethyl)-2'-deoxycytidine (5-hmdC), 5-(formyl)-2'-deoxycytidine (5-fodC), and 5-(carboxyl)-2'-deoxycytidine (5-cadC) are crucial intermediate products of DNA demethylation pathway, which can also act as potential biomarker reflecting the diagnosis and prognosis in multiple tumors. Detecting 5-hmdC, 5-fodC, and 5-cadC in human urine has various advantages including readily available samples and non-invasive to patients. However, few works have reported the detection of 5-fodC and 5-cadC due to their trace amounts...
January 9, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29315835/fto-regulates-the-chemo-radiotherapy-resistance-of-cervical-squamous-cell-carcinoma-cscc-by-targeting-%C3%AE-catenin-through-mrna-demethylation
#20
Shun Zhou, Zhou-Lan Bai, Di Xia, Zhi-Jun Zhao, Ren Zhao, Yan-Yang Wang, Hong Zhe
The role of N6 -methyladenosine (m6 A) demethylase Fat Mass and Obesity-associated protein (FTO) in the regulation of chemo-radiotherapy resistance remains largely unknown. Here, we show that the mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues. FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of β-catenin by reducing m6 A levels in its mRNA transcripts and in turn increases excision repair cross-complementation group 1 (ERCC1) activity...
January 9, 2018: Molecular Carcinogenesis
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