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Rabah B Zo, Ziwen Long
This study was aimed to uncover the effects of miR-124-3p on bladder cancer (BC) by regulating DNA methyltransferase 3B. The expressions of miR-124-3p and DNMT3B mRNA in BC tissues and cell lines were detected using RT-PCR. The expression of DNMT3B in cells was determined using Western blot and immunohistochemistry in tissues. In addition, chromogenic in situ hybridization staining was used to measure the expression of miR-124-3p in tissues. BC cells were transfected with miR-124-3p mimics, miR-124-3p inhibitors, DNMT3B siRNAs, and DNMT3B cDNAs + miR-124-3p mimics...
June 12, 2018: Journal of Cellular Physiology
Xue-Yin Pan, Yang Yang, Hong-Wu Meng, Hai-di Li, Xin Chen, Hui-Min Huang, Fang-Tian Bu, Hai-Xia Yu, Qin Wang, Cheng Huang, Xiao-Ming Meng, Jun Li
The activation of hepatic stellate cells (HSCs) is a central event in the progression of liver fibrosis. Multiple studies proved that DNA methylation might accelerate HSCs activation. However, the specific pathogenesis of liver fibrosis remains not fully addressed. Our laboratory performed Genome methylation screening to find out the methylated gene in mice with liver fibrosis. The pilot experiments showed that the promoter of prostacyclin synthase ( PTGIS ) gene was hypermethylated in CCl4 -induced liver fibrosis mouse model...
2018: Frontiers in Pharmacology
Antonio D Barrera, Elina V García, Dora C Miceli
SummaryDuring preimplantation development, embryos are exposed and have the capacity to respond to different growth factors present in the maternal environment. Among these factors, transforming growth factor β1 (TGF-β1) is a well known modulator of embryonic growth and development. However, its action during the first stages of development, when the embryo transits through the oviduct, has not been yet elucidated. The objective of the present study was to examine the effect of early exposure to exogenous TGF-β1 on embryo development and expression of pluripotency (OCT4, NANOG) and DNA methylation (DNMT1, DNMT3A, DNMT3B) genes in bovine embryos produced in vitro...
June 8, 2018: Zygote: the Biology of Gametes and Early Embryos
Jelena Krasilnikova, Liga Lauberte, Elena Stoyanova, Desislava Abadjieva, Mihail Chervenkov, Mattia Mori, Elisa De Paolis, Vanya Mladenova, Galina Telysheva, Bruno Botta, Elena Kistanova
Oregonin is an open-chain diarylheptanoid isolated from Alnus incana bark that possesses remarkable antioxidant and anti-inflammatory properties, inhibits adipogenesis, and can be used in the prevention of obesity and related metabolic disorders. Here, we aimed to investigate the effects of oregonin on the epigenetic regulation in cells as well as its ability to modulate DNA methylating enzymes expression and mitochondrial DNA (mtDNA) copies. Our results show that oregonin altered the expression of DNA methyltransferases and mtDNA copy numbers in dependency on concentration and specificity of cells genotype...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Tara Nguyen, Gerard E Li, Hui Chen, Charles G Cranfield, Kristine C McGrath, Catherine Anne Gorrie
Electronic cigarette (e-cigarette) use is on the rise worldwide and is particularly attractive to young people and as a smoking substitute by pregnant woman. There is a perception in pregnant woman and women of child-bearing age that the use of e-cigarettes (vaping) is safer than smoking tobacco cigarettes during pregnancy. However, there is little evidence to support this perception. Here, we examined the offspring from mouse dams that had been exposed during and after pregnancy to ambient air (sham) (n=8), e-cigarette aerosols with nicotine (n=8) or e-cigarette aerosols without nicotine (n=8)...
June 4, 2018: Chemical Research in Toxicology
Chunfang Zhao, Xin Li, Bo Han, Lujiang Qu, Changjun Liu, Jiuzhou Song, Ling Lian, Ning Yang
Marek's disease is an oncogenic and lymphoproliferative disease of chickens caused by Marek's disease virus. Hypermethylation or hypomethylation of CpG islands in gene promoter region are involved in the initiation and progression of carcinogenesis. In this study, we analyzed differential methylation levels of upstream region of gga-miR-130b-3p gene between Marek's disease virus-infected tumorous and non-infected spleens. Around the upstream 1 kb of gga-miR-130b-3p gene, two amplicons were designed that covered 616 bp...
May 11, 2018: Oncotarget
Yunfeng Cao, Chunhui Guo, Yanhai Yin, Xin Li, Ling Zhou
The present study aimed to investigate the effect of lysine‑specific demethylase 2 (LSD2) in small cell lung cancer (SCLC) and explore its underlying regulatory mechanism. Cell growth was tested by MTT assay and mRNA and protein expression was determined by quantitative polymerase chain reaction (q‑PCR) and western blot analysis, respectively. Chromatin immunoprecipitation (ChIP) was used to investigate the degree of H3K4me2 enrichment in the promoter region of tissue factor pathway inhibitor‑2 (TFPI‑2)...
May 22, 2018: Molecular Medicine Reports
Yingying Zhang, Mengshu Zhang, Lingjun Li, Bin Wei, Axin He, Likui Lu, Xiang Li, Lubo Zhang, Zhice Xu, Miao Sun
Prenatal hypoxia (PH) is a common pregnancy complication, harmful to brain development. This study investigated whether and how PH affected Wnt pathway in the brain. Pregnant rats were exposed to hypoxia (10.5% O2 ) or normoxia (21% O2 ; Control). Foetal brain weight and body weight were decreased in the PH group, the ratio of brain weight to body weight was increased significantly. Prenatal hypoxia increased mRNA expression of Wnt3a, Wnt7a, Wnt7b and Fzd4, but not Lrp6. Activated β-catenin protein and Fosl1 expression were also significantly up-regulated...
May 28, 2018: Journal of Cellular and Molecular Medicine
Wan Li, Jie Yi, Xiangjin Zheng, Shiwei Liu, Weiqi Fu, Liwen Ren, Li Li, Dave S B Hoon, Jinhua Wang, Guanhua Du
Background: miR-29c has been associated with the progression of many cancers. However, the function and mechanism of miR-29c have not been well investigated in breast cancers. Methods: Real-time quantitative PCR was used to assess expression of miR-29c and DNMT3B mRNA. Western blot and immunochemistry were used to examine the expression of DNA methyltransferase 3B (DNMT3B) protein in breast cancer cells and tissues. The functional roles of miR-29c in breast cancer cells such as proliferation, migration, invasion, colony formation, and 3D growth were evaluated using MTT, transwell chambers, soft agar, and 3D Matrigel culture, respectively...
2018: Clinical Epigenetics
Benjamin G Barwick, Christopher D Scharer, Ryan J Martinez, Madeline J Price, Alexander N Wein, Robert R Haines, Alexander P R Bally, Jacob E Kohlmeier, Jeremy M Boss
B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little is known about how de novo deposition of DNA methylation affects B cell fate and function. Here we show that genetic deletion of the de novo DNA methyltransferases Dnmt3a and Dnmt3b (Dnmt3-deficient) in mouse B cells results in normal B cell development and maturation, but increased cell activation and expansion of the germinal center B cell and plasma cell populations upon immunization...
May 15, 2018: Nature Communications
Palsamy Periyasamy, Annadurai Thangaraj, Ming-Lei Guo, Guoku Hu, Shannon Callen, Shilpa Buch
The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B that were also accompanied by increased global DNA methylation...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yifan Yang, Zhu Jin, Rui Dong, Chao Zheng, Yanlei Huang, Yijie Zheng, Zhen Shen, Gong Chen, Xiaoying Luo, Shan Zheng
Biliary atresia is one of the most common liver disease in infancy. The cause and pathogenesis remain largely unknown. This study aimed to investigate the potential regulatory effect of miR-29b/142-5p on IFN-γ gene methylation. miRNAs microarray was performed on four pairs of liver and blood specimens from biliary atresia and choledochal cysts. We found the overexpression of miR-142-5p and mRNA level of DNA methyltransferase (DNMT) 1, and miR-29b and DNMT3a/DNMT3b were significantly negatively correlated in biliary atresia livers...
May 10, 2018: Cell Death & Disease
Rajnish Kumar Singh, Fengchao Lang, Yonggang Pei, Hem Chandra Jha, Erle S Robertson
Kaposi's sarcoma associated herpesvirus (KSHV) infection stabilizes hypoxia inducible factors (HIFs). The interaction between KSHV encoded factors and HIFs plays a critical role in KSHV latency, reactivation and associated disease phenotypes. Besides modulation of large-scale signaling, KSHV infection also reprograms the metabolic activity of infected cells. However, the mechanism and cellular pathways modulated during these changes are poorly understood. We performed comparative RNA sequencing analysis on cells with stabilized hypoxia inducible factor 1 alpha (HIF1α) of KSHV negative or positive background to identify changes in global and metabolic gene expression...
May 2018: PLoS Pathogens
Ti-Kun Fang, Cheng-Jun Yan, Juan Du
BACKGROUND: Myasthenia gravis (MG) is a progressive autoimmune disease that occurs as a result of the failure of neuromuscular transmission and is characterized by muscle weakness. There has been evidence on the correlations between the genetic predisposition of cytotoxic T lymphocyte and the antigen-4 (CTLA-4) and MG. Thus, the present study was conducted to study is designed to examine the effects of CTLA-4 methylation on the pathogenesis of MG and the expressions of related cytokines...
May 2018: Medicine (Baltimore)
Jia Yu, Bo Qin, Ann M Moyer, Somaira Nowsheen, Tongzheng Liu, Sisi Qin, Yongxian Zhuang, Duan Liu, Shijia W Lu, Krishna R Kalari, Daniel W Visscher, John A Copland, Sarah A McLaughlin, Alvaro Moreno-Aspitia, Donald W Northfelt, Richard J Gray, Zhenkun Lou, Vera J Suman, Richard Weinshilboum, Judy C Boughey, Matthew P Goetz, Liewei Wang
Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis that lacks targeted therapies, especially in patients with chemotherapy-resistant disease. Since DNA methylation-induced silencing of tumor suppressors is common in cancer, reversal of promoter DNA hypermethylation by 5-aza-2'-deoxycytidine (decitabine), an FDA-approved DNA methyltransferase (DNMT) inhibitor, has proven effective in treating hematological neoplasms. However, its antitumor effect varies in solid tumors, stressing the importance of identifying biomarkers predictive of therapeutic response...
April 30, 2018: Journal of Clinical Investigation
Saghar Saeedabadi, Amir Hossein Abazari-Kia, Hoda Rajabi, Kazem Parivar, Mohammad Salehi
Background: DNA methylation is one the epigenetic mechanisms, which is critically involved in gene expression. This phenomenon is mediated by DNA methyl-transferases and is affected by environmental stress, including in vitro maturation (IVM) of oocytes. Melatonin, as an antioxidant, may theoretically be involved in epigenetic regulation via reductions of reactive oxygen species. This study was performed to investigate DNA methylation and the possibility of goat oocyte development after treatment with different concentrations of melatonin...
July 2018: International Journal of Fertility & Sterility
Xiao-Xia Yu, Yun-Hua Liu, Xiao-Man Liu, Pei-Chao Wang, Shuai Liu, Jia-Kun Miao, Zhi-Qiang Du, Cai-Xia Yang
L-ascorbic acid (Vitamin C) can enhance the meiotic maturation and developmental competence of porcine oocytes, but the underlying molecular mechanism remains obscure. Here we show the role of ascorbic acid in regulating epigenetic status of both nucleic acids and chromatin to promote oocyte maturation and development in pigs. Supplementation of 250 μM L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P) during in vitro maturation significantly enhanced the nuclear maturation (as indicated by higher rate of first polar body extrusion and increased Bmp15 mRNA level), reduced level of reactive oxygen species, and promoted developmental potency (higher cleavage and blastocyst rates of parthenotes, and decreased Bax and Caspase3 mRNA levels in blastocysts) of pig oocytes...
April 17, 2018: Scientific Reports
Tahereh Rahiminia, Ehsan Farashahi Yazd, Farzaneh Fesahat, Mohammad Reza Moein, Ali Mohammad Mirjalili, Ali Reza Talebi
Objective: To investigate sperm chromatin/DNA integrity, global DNA methylation, and DNMT mRNA transcription in men with oligoasthenoteratozoospermia (OAT) compared with normozoospermic men. Methods: Semen samples from 32 OAT patients who comprised the case group and 32 normozoospermic men who comprised the control group were isolated and purified using a standard gradient isolation procedure according to World Health Organization criteria. DNMT1 , DNMT3A , and DNMT3B transcripts were then compared between groups using real-time quantitative reverse-transcription polymerase chain reaction...
March 2018: Clinical and Experimental Reproductive Medicine
Guillaume Velasco, Giacomo Grillo, Nizar Touleimat, Laure Ferry, Ivana Ivkovic, Florence Ribierre, Jean-François Deleuze, Sophie Chantalat, Capucine Picard, Claire Francastel
Alterations of DNA methylation landscapes and machinery are a hallmark of many human diseases. A prominent case is the ICF syndrome, a rare autosomal recessive immunological/neurological disorder diagnosed by the loss of DNA methylation at (peri)centromeric repeats and its associated chromosomal instability. It is caused by mutations in the de novo DNA methyltransferase DNMT3B in about half of the patients (ICF1). In the remainder, the striking identification of mutations in factors devoid of DNA methyltransferase activity, ZBTB24 (ICF2), CDCA7 (ICF3) or HELLS (ICF4), raised key questions about common or distinguishing DNA methylation alterations downstream of these mutations and hence, about the functional link between the four factors...
April 12, 2018: Human Molecular Genetics
David Alvarez-Ponce, María Torres-Sánchez, Felix Feyertag, Asmita Kulkarni, Taylen Nappi
DNA methylation is mediated by a conserved family of DNA methyltransferases (Dnmts). The human genome encodes three active Dnmts (Dnmt1, Dnmt3a and Dnmt3b), the tRNA methyltransferase Dnmt2, and the regulatory protein Dnmt3L. Despite their high degree of conservation among different species, genes encoding Dnmts have been duplicated and/or lost in multiple lineages throughout evolution, indicating that the DNA methylation machinery has some potential to undergo evolutionary change. However, little is known about the extent to which this machinery, or the methylome, varies among vertebrates...
2018: PloS One
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