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https://www.readbyqxmd.com/read/28816066/stressing-the-epi-genome-dealing-with-ros-in-cancer
#1
Akshay V Bhat, Shainan Hora, Ananya Pal, Sudhakar Jha, Reshma Taneja
SIGNIFICANCE: Growing evidence indicates cross-talk between Reactive oxygen species (ROS) and several key epigenetic processes like DNA methylation, histone modifications and miRNAs in normal physiology and human pathologies including cancer. This review focuses on how ROS-induced oxidative stress, metabolic intermediates and epigenetic processes influence each other in various cancers. Recent Advances: ROS alters chromatin structure and metabolism which impact the epigenetic landscape in cancer cells...
August 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28812986/epigenome-aberrations-emerging-driving-factors-of-the-clear-cell-renal-cell-carcinoma
#2
REVIEW
Ali Mehdi, Yasser Riazalhosseini
Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28800870/recent-advances-in-her2-positive-breast-cancer-epigenetics-susceptibility-and-therapeutic-strategies
#3
REVIEW
Heena Singla, Abhilash Ludhiadch, Raman Preet Kaur, Harish Chander, Vinod Kumar, Anjana Munshi
HER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways. Understanding of epigenomic regulation of HER2 overexpression and signaling may help uncover the unmatchable physiology of HER2 gene/protein...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28795861/lnc00673-errlr01-is-a-prognostic-indicator-of-overall-survival-in-breast-cancer
#4
Ubaidat Abdul-Rahman, Balázs Gyoörffy, Brian D Adams
LncRNAs are novel noncoding RNAs involved in the epigenetic regulation of gene expression by recruiting ribonucleoprotein complexes to specific genomic loci to initiate histone methylation and/or other chromatin modifications. LncRNAs themselves function as tumor suppressors or oncogenes, depending on the gene regulatory networks they govern. We identified lnc00673 (ERRLR01) as a marker of overall survival (OS) in breast cancer patients. Specifically, ERRLR01 levels were elevated in triple-negative breast cancer (TNBC) as compared to Luminal- A, Luminal-B, and HER2 breast cancer subtypes...
August 10, 2017: Transcription
https://www.readbyqxmd.com/read/28794818/electrophoretic-stretching-and-imaging-of-single-native-chromatin-fibers-in-nanoslits
#5
Jia-Wei Yeh, Kylan Szeto
Stretching single chromosomal DNA fibers in nanofluidic devices has become a valuable tool for studying the genome and more recently the epigenome. Although nanofluidic technology has been extensively used in single molecular DNA analysis, compared to bare DNA, much less work has been done to elongate chromatin, and only a few studies utilize more biologically relevant samples such as native eukaryotic chromatin. Here, we provide a method for stretching and imaging individual chromatin fibers within a micro- and nanofluidic device...
July 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28783137/acetylation-and-methylation-related-epigenetic-proteins-in-the-context-of-their-targets
#6
REVIEW
Nasir Javaid, Sangdun Choi
The nucleosome surface is covered with multiple modifications that are perpetuated by eight different classes of enzymes. These enzymes modify specific target sites both on DNA and histone proteins, and these modifications have been well identified and termed "epigenetics". These modifications play critical roles, either by affecting non-histone protein recruitment to chromatin or by disturbing chromatin contacts. Their presence dictates the condensed packaging of DNA and can coordinate the orderly recruitment of various enzyme complexes for DNA manipulation...
August 7, 2017: Genes
https://www.readbyqxmd.com/read/28761088/shift-of-emt-gradient-in-3d-spheroid-mscs-for-activation-of-mesenchymal-niche-function
#7
Sohee Jeon, Ho-Sun Lee, Ga-Young Lee, Gyeongsin Park, Tae-Min Kim, Jihye Shin, Cheolju Lee, Il-Hoan Oh
Despite the wide use of mesenchymal stromal cells (MSCs) for paracrine support in clinical trials, their variable and heterogeneous supporting activity pose major challenges. While three-dimensional (3D) MSC cultures are emerging as alternative approaches, key changes in cellular characteristics during 3D-spheroid formation remain unclear. Here, we show that MSCs in 3D spheroids undergo further progression towards the epithelial-mesenchymal transition (EMT), driven by upregulation of EMT-promoting microRNAs and suppression of EMT-inhibitory miRNAs...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759046/ezh2-mediated-upregulation-of-ros1-oncogene-promotes-oral-cancer-metastasis
#8
C-H Shih, Y-J Chang, W-C Huang, T-H Jang, H-J Kung, W-C Wang, M-H Yang, M-C Lin, S-F Huang, S-W Chou, E Chang, H Chiu, T-Y Shieh, Y-J Chen, L-H Wang, L Chen
Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28754290/molecular-epigenetic-targets-for-liver-diseases-current-challenges-and-future-prospects
#9
REVIEW
Robert Zeidler, Bruno Leonardo de Freitas Soares, Augustinus Bader, Shibashish Giri
Advanced chemotherapy fails to treat liver cancer but recent progress in understanding epigenetic modifications have witnessed promising clinical outcomes. Epigenetic alteration is the alteration of epigenomes (surrounding histone proteins) without changing the DNA sequence. Such epigenetic mechanisms include histone modifications such as methylation, acetylation, phosphorylation and sumoylation followed by changes in the genomic architecture. Current studies involving the understanding of small RNA molecules such as noncoding RNA and microRNA in modulating the chromatin architecture are explained in depth here, along with effects of some novel compounds from recent preclinical and clinical evidence...
July 25, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28741489/epigenomic-consequences-of-coding-and-noncoding-driver-mutations
#10
REVIEW
Xiaosai Yao, Manjie Xing, Wen Fong Ooi, Patrick Tan, Bin Tean Teh
Chromatin alterations are integral to the pathogenic process of cancer, as demonstrated by recent discoveries of frequent mutations in chromatin-modifier genes and aberrant DNA methylation states in different cancer types. Progress is being made on elucidating how chromatin alterations, and how proteins catalyzing these alterations, mechanistically contribute to tissue-specific tumorigenesis. In parallel, technologies enabling the genome-wide profiling of histone modifications have revealed the existence of noncoding driver genetic alterations in cancer...
October 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28717873/orchestration-of-h3k27-methylation-mechanisms-and-therapeutic-implication
#11
REVIEW
Mei-Ren Pan, Ming-Chuan Hsu, Li-Tzong Chen, Wen-Chun Hung
Histone proteins constitute the core component of the nucleosome, the basic unit of chromatin. Chemical modifications of histone proteins affect their interaction with genomic DNA, the accessibility of recognized proteins, and the recruitment of enzymatic complexes to activate or diminish specific transcriptional programs to modulate cellular response to extracellular stimuli or insults. Methylation of histone proteins was demonstrated 50 years ago; however, the biological significance of each methylated residue and the integration between these histone markers are still under intensive investigation...
July 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#12
Carolina J Simoes da Silva, Sol Fereres, Rocío Simón, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
September 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28711634/role-of-epigenetic-modulation-in-cancer-stem-cell-fate
#13
REVIEW
Abhijeet Deshmukh, Mudra Binju, Frank Arfuso, Philip Newsholme, Arun Dharmarajan
A sub-population of the tumor micro-environment consists of cancer stem cells (CSCs), which are responsible for the initiation and recurrence of cancer. Recently, epigenetic processes such as DNA methylation, histone modification, and chromatin remodeling have been found to be involved in inducing epigenetic factors in CSCs. Most of these processes, such as DNA methylation, generally occur in the genome that is rich in Cytosine-Guanine repeat sequences, also known as CpG islands, which are distributed throughout the human genome...
July 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28709969/role-of-epigenome-in-tumorigenesis-and-drug-resistance
#14
Qidong Hu, Gyeong Hun Baeg
The last few decades have witnessed a tremendous advancement in understanding the genetic basis of major human diseases such as cancer. Intriguingly, there is also an evergrowing body of evidence that suggest the critical role of epigenetic regulation in pathogenesis. In contrast to genetic mechanisms often associated with changes in DNA sequence, epigenetics generally refers to the regulation of gene expression featuring alterations in histone modification, DNA methylation, chromatin conformation and noncoding RNAs, with the first two categories being the best-characterized so far...
July 11, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28705657/role-of-glutathione-in-the-regulation-of-epigenetic-mechanisms-in-disease
#15
REVIEW
José Luis García-Giménez, Carlos Romá-Mateo, Gisselle Pérez-Machado, Lorena Peiró-Chova, Federico V Pallardó
Epigenetics is a rapidly growing field that studies gene expression modifications not involving changes in the DNA sequence. Histone H3, one of the basic proteins in the nucleosomes that make up chromatin, is S-glutathionylated in mammalian cells and tissues, making Gamma-L-glutamyl-L-cysteinylglycine, glutathione (GSH), a physiological antioxidant and second messenger in cells, a new post-translational modifier of the histone code that alters the structure of the nucleosome. However, the role of GSH in the epigenetic mechanisms likely goes beyond a mere structural function...
July 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28704968/epigenetic-modifications-and-head-and-neck-cancer-implications-for-tumor-progression-and-resistance-to-therapy
#16
REVIEW
Rogerio M Castilho, Cristiane H Squarize, Luciana O Almeida
Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28704917/the-role-of-hypoxia-on-the-acquisition-of-epithelial-mesenchymal-transition-and-cancer-stemness-a-possible-link-to-epigenetic-regulation
#17
REVIEW
Chang Dong Yeo, Nahyeon Kang, Su Yeon Choi, Bit Na Kim, Chan Kwon Park, Jin Woo Kim, Young Kyoon Kim, Seung Joon Kim
A hypoxic microenvironment leads to cancer progression and increases the metastatic potential of cancer cells within tumors via epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. The hypoxic response pathway can occur under oxygen tensions of < 40 mmHg through hypoxia-inducible factors (HIFs), which are considered key mediators in the adaptation to hypoxia. Previous studies have shown that cellular responses to hypoxia are required for EMT and cancer stemness maintenance through HIF-1α and HIF-2α...
July 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28689146/chemical-modulators-for-epigenome-reader-domains-as-emerging-epigenetic-therapies-for-cancer-and-inflammation
#18
REVIEW
Nilesh Zaware, Ming-Ming Zhou
Site-specific lysine acetylation and methylation on histones are critical post-translational modifications (PTMs) that govern ordered gene transcription in chromatin. Mis-regulation of these histone PTM-mediated processes has been shown to be associated with human diseases. Since the 2010 landmark reports of small molecules (+)-JQ1 and I-BET762 that target the acetyl-lysine 'reader' Bromodomain and Extra Terminal domain (BET) proteins, there have been relentless efforts to develop epigenetic therapy with small molecules to modulate molecular interactions of epigenome reader domain proteins with PTMs...
July 6, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28677817/inhibition-of-the-hdac-suv39-g9a-pathway-restores-the-expression-of-dna-damage-dependent-major-histocompatibility-complex-class%C3%A2-i-related-chain%C3%A2-a%C3%A2-and%C3%A2-b-in-cancer-cells
#19
Nakako Izumi Nakajima, Atsuko Niimi, Mayu Isono, Takahiro Oike, Hiro Sato, Takashi Nakano, Atsushi Shibata
Immunotherapy is expected to be promising as a next generation cancer therapy. Immunoreceptors are often activated constitutively in cancer cells, however, such levels of ligand expression are not effectively recognized by the native immune system due to tumor microenvironmental adaptation. Studies have demonstrated that natural-killer group 2, member D (NKG2D), a major activating immunoreceptor, responds to DNA damage. The upregulation of major histocompatibility complex class I-related chain A and B (MICA/B) (members of NKG2D ligands) expression after DNA damage is associated with NK cell-mediated killing of cancer cells...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28650470/signaling-coupled-epigenomic-regulation-of-gene-expression
#20
REVIEW
R Kumar, S Deivendran, T R Santhoshkumar, M R Pillai
Inheritance of genomic information independent of the DNA sequence, the epigenetics, as well as gene transcription are profoundly shaped by serine/threonine and tyrosine signaling kinases and components of the chromatin remodeling complexes. To precisely respond to a changing external milieu, human cells efficiently translate upstream signals into post-translational modifications (PTMs) on histones and coregulators such as corepressors, coactivators, DNA-binding factors and PTM modifying enzymes. Because a protein with multiple residues for putative PTMs is expected to undergo more than one PTM in cells stimulated with growth factors, the outcome of combinational PTM codes on histones and coregulators is profoundly shaped by regulatory interplays between PTMs...
June 26, 2017: Oncogene
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