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https://www.readbyqxmd.com/read/29777275/overexpression-of-abcb4-contributes-to-acquired-doxorubicin-resistance-in-breast-cancer-cells-in-vitro
#1
Jia-Feng Huang, Chun-Jie Wen, Guo-Zhi Zhao, Yi Dai, Ying Li, Lan-Xiang Wu, Hong-Hao Zhou
PURPOSE: Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism. METHODS: In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry...
May 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29774131/methylation-of-dna-and-chromatin-as-a-mechanism-of-oncogenesis-and-therapeutic-target-in-neuroblastoma
#2
REVIEW
Ram Mohan Ram Kumar, Nina Felice Schor
Neuroblastoma (NB), a developmental cancer, is often fatal, emphasizing the need to understand its pathogenesis and identify new therapeutic targets. The heterogeneous pathological and clinical phenotype of NB underscores the cryptic biological and genetic features of this tumor that result in outcomes ranging from rapid progression to spontaneous regression. Despite recent genome-wide mutation analyses, most primary NBs do not harbor driver mutations, implicating epigenetically-mediated gene regulatory mechanisms in the initiation and maintenance of NB...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#3
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773832/distinct-epigenetic-landscapes-underlie-the-pathobiology-of-pancreatic-cancer-subtypes
#4
Gwen Lomberk, Yuna Blum, Rémy Nicolle, Asha Nair, Krutika Satish Gaonkar, Laetitia Marisa, Angela Mathison, Zhifu Sun, Huihuang Yan, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Tamas Ordog, Jeong-Heon Lee, Gavin Oliver, Eric Klee, Vincent Moutardier, Odile Gayet, Benjamin Bian, Pauline Duconseil, Marine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien De Reyniès, Nelson Dusetti, Juan Iovanna, Raul Urrutia
Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773653/inhibition-of-protein-arginine-methyltransferase-5-enhances-hepatic-mitochondrial-biogenesis
#5
Lei Huang, Jehnan Liu, Xiao-Ou Zhang, Katelyn Sibley, Sonia M Najjar, Mary M Lee, Joae Qiong Wu
Protein arginine methyltransferase 5 (PRMT5) regulates gene expression either transcriptionallyly by symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3, or at the post-translational level by methylation of non-histone target proteins. While emerging evidence suggests that PRMT5 functions as an oncogene, its role in metabolic diseases is not well defined. We investigated the role of PRMT5 in promoting high fat-induced hepatic steatosis. High fat diet up-regulated PRMT5 levels in the liver, but not in other metabolically relevant tissues such as skeletal muscle or white and brown adipose tissue...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29773426/stem-cell-transcription-factor-sox2-in-synovial-sarcoma-and-other-soft-tissue-tumors
#6
Heba Zayed, Iver Petersen
BACKGROUND: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29769529/methionine-metabolism-influences-genomic-architecture-and-gene-expression-through-h3k4me3-peak-width
#7
Ziwei Dai, Samantha J Mentch, Xia Gao, Sailendra N Nichenametla, Jason W Locasale
Nutrition and metabolism are known to influence chromatin biology and epigenetics through post-translational modifications, yet how this interaction influences genomic architecture and connects to gene expression is unknown. Here we consider, as a model, the metabolically-driven dynamics of H3K4me3, a histone methylation mark that is known to encode information about active transcription, cell identity, and tumor suppression. We analyze the genome-wide changes in H3K4me3 and gene expression in response to alterations in methionine availability in both normal mouse physiology and human cancer cells...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29768411/cytoskeleton-structure-and-total-methylation-of-mouse-cardiac-and-lung-tissue-during-space-flight
#8
Irina V Ogneva, Sergey S Loktev, Vladimir N Sychev
The purpose of this work was to evaluate the protein and mRNA expression levels of multiple cytoskeletal proteins in the cardiac and lung tissue of mice that were euthanized onboard the United States Orbital Segment of the International Space Station 37 days after the start of the SpaceX-4 mission (September 2014, USA). The results showed no changes in the cytoskeletal protein content in the cardiac and lung tissue of the mice, but there were significant changes in the mRNA expression levels of the associated genes, which may be due to an increase in total genome methylation...
2018: PloS One
https://www.readbyqxmd.com/read/29765862/genomic-imprinting-and-the-regulation-of-postnatal-neurogenesis
#9
REVIEW
Anna Lozano-Ureña, Raquel Montalbán-Loro, Anne C Ferguson-Smith, Sacri R Ferrón
Most genes required for mammalian development are expressed from both maternally and paternally inherited chromosomal homologues. However, there are a small number of genes known as " imprinted genes " that only express a single allele from one parent, which is repressed on the gene from the other parent. Imprinted genes are dependent on epigenetic mechanisms such as DNA methylation and post-translational modifications of the DNA-associated histone proteins to establish and maintain their parental identity...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29765857/dna-methylation-and-adult-neurogenesis
#10
REVIEW
Emily M Jobe, Xinyu Zhao
The role of DNA methylation in brain development is an intense area of research because the brain has particularly high levels of CpG and mutations in many of the proteins involved in the establishment, maintenance, interpretation, and removal of DNA methylation impact brain development and/or function. These include DNA methyltransferase (DNMT), Ten-Eleven Translocation (TET), and Methyl-CpG binding proteins (MBPs). Recent advances in sequencing breadth and depth as well the detection of different forms of methylation have greatly expanded our understanding of the diversity of DNA methylation in the brain...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29765031/comprehensive-epigenetic-landscape-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#11
Rizi Ai, Teresina Laragione, Deepa Hammaker, David L Boyle, Andre Wildberg, Keisuke Maeshima, Emanuele Palescandolo, Vinod Krishna, David Pocalyko, John W Whitaker, Yuchen Bai, Sunil Nagpal, Kurtis E Bachman, Richard I Ainsworth, Mengchi Wang, Bo Ding, Percio S Gulko, Wei Wang, Gary S Firestein
Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764865/hp1%C3%AE-promotes-lung-adenocarcinoma-by-downregulating-the-transcription-repressive-regulators-ncor2-and-zbtb7a
#12
Hunain Alam, Na Li, Shilpa S Dhar, Sarah J Wu, Jie Lv, Kaifu Chen, Elsa R Flores, Laura Baseler, Min Gyu Lee
Lung adenocarcinoma (LUAD) is a major form of lung cancer, which is the leading cause of cancer death. Histone methylation reader proteins mediate the effect of histone methylation, a hallmark of epigenetic and transcriptional regulation of gene expression. However, their roles in LUAD are poorly understood. Here our bioinformatic screening and analysis in search of an LUAD-promoting histone methylation reader protein show that heterochromatin protein 1γ (HP1γ; also called CBX3) is among the most frequently overexpressed and amplified histone reader proteins in human LUAD, and that high HP1γ mRNA levels are associated with poor prognosis in LUAD patients...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764658/transgenerational-effects-of-insecticides-implications-for-rapid-pest-evolution-in-agroecosystems
#13
REVIEW
Kristian Brevik, Leena Lindström, Stephanie D McKay, Yolanda H Chen
Although pesticides are a major selective force in driving the evolution of insect pests, the evolutionary processes that give rise to insecticide resistance remain poorly understood. Insecticide resistance has been widely observed to increase with frequent and intense insecticide exposure, but can be lost following the relaxation of insecticide use. One possible but rarely explored explanation is that insecticide resistance may be associated with epigenetic modifications, which influence the patterning of gene expression without changing underlying DNA sequence...
April 2018: Current Opinion in Insect Science
https://www.readbyqxmd.com/read/29763912/-a-succinate-ether-derivative-of-tocotrienol-enhances-dickkopf-1-gene-expression-through-epigenetic-alterations-in-malignant-mesothelioma-cells
#14
Ayami Sato, Haruka Ueno, Momoka Fusegi, Saki Kaneko, Kakeru Kohno, Nantiga Virgona, Akira Ando, Yuko Sekine, Tomohiro Yano
BACKGROUND: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1)...
May 15, 2018: Pharmacology
https://www.readbyqxmd.com/read/29763383/eb-2017-article-soy-protein-isolate-feeding-does-not-result-in-reproductive-toxicity-in-the-pre-pubertal-rat-testis
#15
Martin Jj Ronis, Horacio Gomez-Acevedo, Kartik Shankar, Neha Sharma, Michael Blackburn, Rohit Singhal, Kelly E Mercer, Thomas M Badger
The isoflavone phytoestrogens found in the soy protein isolate used in soy infant formulas have been shown to have estrogenic actions in the developing male reproductive tract resulting in reproductive toxicity. However, few studies have examined potential estrogenicity of soy protein isolate as opposed to that of pure isoflavones. In this study, we fed weanling male Sprague-Dawley rats a semi-purified diet with casein or soy protein isolate as the sole protein source from postnatal day 21 to 33. Additional groups were fed casein or soy protein isolate and treated s...
May 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29763382/kdm2b-is-a-histone-h3k79-demethylase-and-induces-transcriptional-repression-via-sirtuin-1-mediated-chromatin-silencing
#16
Joo-Young Kang, Ji-Young Kim, Kee-Beom Kim, Jin Woo Park, Hana Cho, Ja Young Hahm, Yun-Cheol Chae, Daehwan Kim, Hyun Kook, Sangmyeong Rhee, Nam-Chul Ha, Sang-Beom Seo
The methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and is prominent in actively transcribed regions of the genome; however, demethylase of H3K79 remains unknown despite intensive research. Here, we show that KDM2B, also known as FBXL10 and a member of the Jumonji C family of proteins known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via occupancy of promoters and demethylation of H3K79...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29762370/molecular-regulations-of-mucosal-maltase-expressions
#17
Toshinao Goda, Kazue Honma
Two major α-glucosidase (maltase) genes, sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM), respectively, are expressed in the small intestine. In this review, we have summarized whether jejunal expression of these maltase genes is regulated by dietary manipulations, which may affect carbohydrate availability from the luminal side, through changes in the binding of transcription factors and/or histone code on these genes. Studies using a model of mice fed either a low-starch or a high-starch diet for 7 days, found the mRNA levels of SI, MGAM, and Na-glucose cotransporter (SGLT1) genes in the jejunum to be increased in parallel by feeding a high-starch diet...
June 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29760279/histone-h3k27-methylation-is-required-for-nhej-and-genome-stability-by-modulating-the-dynamics-of-fancd2-on-chromatin
#18
Ye Zhang, Jian-Feng Chang, Jin Sun, Lu Chen, Xiao-Mei Yang, Huan-Yin Tang, Yuan-Ya Jing, Xuan Kang, Zhi-Min He, Jun-Yu Wu, Hui-Min Wei, Da-Liang Wang, Rong-Gang Xu, Rui-Bao Zhu, Ying Shen, Shi-Yang Zeng, Chen Wang, Kui-Nan Liu, Yong Zhang, Zhi-Ying Mao, Ci-Zhong Jiang, Fang-Lin Sun
Dysregulation of homeostatic balance in di- and tri-methyl H3K27 levels or that caused by mis-sense mutations of histone H3 (H3K27M) was reported to be associated with various types of cancers. In this study, we found that reduction in H3K27me2/3 caused by H3.1K27M, a mutation of H3 variants found in DIPG patients, dramatically attenuated the presence of 53BP1 foci and NHEJ repair capability in HDF cells. H3.1K27M cells showed increased rates of genomic insertions/deletions (In/Dels) and copy number variations (CNVs), as well as augmented p53-dependent apoptotic cells...
May 14, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29759640/enhancer-of-zeste-homolog-2-ezh2-regulates-tumor-angiogenesis-and-predicts-recurrence-and-prognosis-of-intrahepatic-cholangiocarcinoma
#19
Shigeki Nakagawa, Hirohisa Okabe, Mayuko Ouchi, Ryuma Tokunaga, Naoki Umezaki, Takaaki Higashi, Takatoshi Kaida, Kota Arima, Yuki Kitano, Hideyuki Kuroki, Kosuke Mima, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Yo-Ichi Yamashita, Akira Chikamoto, Hideo Baba
BACKGROUND: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulates tumor malignancy by gene silencing via histone methylation. In this study we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC). METHODS: The influence of EZH2 on tumor angiogenesis was examined by bioinformatics analysis of a public database. We also assessed the correlation between EZH2 and vasohibin 1 (VASH1) expression in 47 patients with ICC by immunohistochemical (IHC) staining and in vitro gene silencing assays...
May 11, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/29755986/implications-of-cellular-aging-in-cardiac-reprogramming
#20
Fabiana Passaro, Gianluca Testa
Aging is characterized by a chronic functional decline of organ systems which leads to tissue dysfunction over time, representing a risk factor for diseases development, including cardiovascular. The aging process occurring in the cardiovascular system involves heart and vessels at molecular and cellular level, with subsequent structural modifications and functional impairment. Several modifications involved in the aging process can be ascribed to cellular senescence, a biological response that limits the proliferation of damaged cells...
2018: Frontiers in Cardiovascular Medicine
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