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Cancer progression chromatin

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https://www.readbyqxmd.com/read/28718414/epigenetics-and-cancer-stem-cells-unleashing-hijacking-and-restricting-cellular-plasticity
#1
REVIEW
Elanor N Wainwright, Paola Scaffidi
Epigenetic mechanisms have emerged as key players in cancer development which affect cellular states at multiple stages of the disease. During carcinogenesis, alterations in chromatin and DNA methylation resulting from genetic lesions unleash cellular plasticity and favor oncogenic cellular reprogramming. At later stages, during cancer growth and progression, additional epigenetic changes triggered by interaction with the microenvironment modulate cancer cell phenotypes and properties, and shape tumor architecture...
May 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717873/orchestration-of-h3k27-methylation-mechanisms-and-therapeutic-implication
#2
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/28714515/elncrna1-a-long-non-coding-rna-that-is-transcriptionally-induced-by-oestrogen-promotes-epithelial-ovarian-cancer-cell-proliferation
#3
Jun-Jun Qiu, Xiao-Dan Zhang, Xiao-Yan Tang, Ting-Ting Zheng, Ying Zhang, Ke-Qin Hua
Previously, the novel oestrogen (E2)-upregulated lncRNA TC0101441, was identified by us, via microarray analysis. However, the detailed mechanism by which E2 upregulates TC0101441 and the role of TC0101441 in epithelial ovarian cancer (EOC) progression have not been elucidated. In the present study, we further analysed TC0101441, which we designated oestrogen-induced long non-coding RNA-1 (ElncRNA1). We showed that E2 transcriptionally upregulates ElncRNA1 through the oestrogen receptor α (ERα)-oestrogen response element (ERE) pathway using RNA stability assays, bioinformatics-based searches for ERE binding sites, chromatin immunoprecipitation (ChIP) assays and dual luciferase reporter assays...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28714471/progression-through-mitosis-promotes-parp-inhibitor-induced-cytotoxicity-in-homologous-recombination-deficient-cancer-cells
#4
Pepijn M Schoonen, Francien Talens, Colin Stok, Ewa Gogola, Anne Margriet Heijink, Peter Bouwman, Floris Foijer, Madalena Tarsounas, Sohvi Blatter, Jos Jonkers, Sven Rottenberg, Marcel A T M van Vugt
Mutations in homologous recombination (HR) genes BRCA1 and BRCA2 predispose to tumorigenesis. HR-deficient cancers are hypersensitive to Poly (ADP ribose)-polymerase (PARP) inhibitors, but can acquire resistance and relapse. Mechanistic understanding how PARP inhibition induces cytotoxicity in HR-deficient cancer cells is incomplete. Here we find PARP inhibition to compromise replication fork stability in HR-deficient cancer cells, leading to mitotic DNA damage and consequent chromatin bridges and lagging chromosomes in anaphase, frequently leading to cytokinesis failure, multinucleation and cell death...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#5
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, 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...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28709969/role-of-epigenome-in-tumorigenesis-and-drug-resistance
#6
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/28704968/epigenetic-modifications-and-head-and-neck-cancer-implications-for-tumor-progression-and-resistance-to-therapy
#7
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
#8
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/28696308/tsrna-signatures-in-cancer
#9
Veronica Balatti, Giovanni Nigita, Dario Veneziano, Alessandra Drusco, Gary S Stein, Terri L Messier, Nicholas H Farina, Jane B Lian, Luisa Tomasello, Chang-Gong Liu, Alexey Palamarchuk, Jonathan R Hart, Catherine Bell, Mariantonia Carosi, Edoardo Pescarmona, Letizia Perracchio, Maria Diodoro, Andrea Russo, Anna Antenucci, Paolo Visca, Antonio Ciardi, Curtis C Harris, Peter K Vogt, Yuri Pekarsky, Carlo M Croce
Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the ts-4521/3676 cluster (now called "ts-101" and "ts-53," respectively), ts-46, and ts-47 are down-regulated in these malignancies...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28687616/post-transcriptional-regulation-of-parg-mrna-by-hur-facilitates-dna-repair-and-resistance-to-parp-inhibitors
#10
Saswati N Chand, Mahsa Zarei, Matthew J Schiewer, Akshay R Kamath, Carmella Romeo, Shruti Lal, Joseph A Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric Londin, Wei Jiang, Nicole Meisner-Kober, Michael J Pishvaian, Karen E Knudsen, Charles J Yeo, John M Pascal, Jordan M Winter, Jonathan R Brody
The majority of pancreatic ductal adenocarcinomas (PDA) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here we show that CRISPR-Cas9-mediated silencing of the HuR locus increases the relative sensitivity of PDA cells to PARP inhibitors (PARPi). PDA cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, polyADP-ribose glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3' untranslated region (UTR)...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28685067/molecular-genetics-complexity-impeding-research-progress-in-breast-and-ovarian-cancers
#11
Ishita Gupta, Ikram Burney, Mansour S Al-Moundhri, Yahya Tamimi
Breast and ovarian cancer are heterogeneous diseases. While breast cancer accounts for 25% of cancers worldwide, ovarian cancer accounts for 3.5% of all cancers and it is considered to be the most lethal type of cancer among women. In Oman, breast cancer accounts for 25% and ovarian cancer for 4.5% of all cancer cases. Various risk factors, including variable biological and clinical traits, are involved in the onset of breast and ovarian cancer. Although highly developed diagnostic and therapeutic methods have paved the way for better management, targeted therapy against specific biomarkers has not yet shown any significant improvement, particularly in triple-negative breast cancer and epithelial ovarian cancer, which are associated with high mortality rates...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28683467/rbm38-is-involved-in-tgf-%C3%AE-induced-epithelial-to-mesenchymal-transition-by-stabilising-zonula-occludens-1-mrna-in-breast-cancer
#12
Jing Wu, Xu-Jie Zhou, Xi Sun, Tian-Song Xia, Xiao-Xia Li, Liang Shi, Lei Zhu, Wen-Bin Zhou, Ji-Fu Wei, Qiang Ding
BACKGROUND: The transforming growth factor-β (TGF-β) pathway plays a vital role in driving cancer cell epithelial-mesenchymal transition (EMT). Zonula occludens-1 (ZO-1), which is downregulated in response to TGF-β, is able to control endothelial cell-cell tension, cell migration, and barrier formation. However, the molecular mechanism of how TGF-β regulates ZO-1 expression remains unclear. METHODS: Breast cancer cells were treated with TGF-β to induce an EMT progress...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28681984/brd4-promotes-gastric-cancer-progression-through-the-transcriptional-and-epigenetic-regulation-of-c-myc
#13
Mingchen Ba, Hui Long, Zhaofei Yan, Shuai Wang, Yinbing Wu, Yinuo Tu, Yuanfeng Gong, Shuzhong Cui
Although the significance of BRD4 in the epigenetic memory and cancer genesis has been intensively investigated, little is known about its function and potential roles during the generation and progression of gastric cancer. We report here that BRD4 increases the proliferation and represses the apoptosis of gastric cancer cells through activating c-MYC via transcriptional and epigenetic regulation mechanisms. Expression analyses in both small and large cohort of sample show that BRD4 is highly expressed in gastric cancer tissues/cells when compared with the adjacent non-tumor tissues/normal cells...
July 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28671020/the-wnt-%C3%AE-catenin-and-pi3k-akt-signaling-pathways-promote-emt-in-gastric-cancer-by-epigenetic-regulation-via-h3-lysine-27-acetylation
#14
Yue Song, Zhao-Xia Li, Xi Liu, Rui Wang, Li-Wei Li, Qingyu Zhang
In this study, we investigated the underlying mechanism of the phosphoinositide 3-kinase/Akt- and Wnt/β-catenin-mediated promotion of epithelial-to-mesenchymal transition by epigenetic regulation of histone acetylation in gastric cancer. First, we used immunohistochemistry to detect the expression of phosphorylated Akt, phosphorylated glycogen synthase kinase 3 beta, and β-catenin in gastric cancer tissues and adjacent tissues. In addition, we confirmed that the phosphoinositide 3-kinase/Akt and Wnt/β-catenin signaling pathways were correlated with tumorigenesis, progression, and maintenance of gastric cancer using the phosphoinositide 3-kinase inhibitor LY294002 and an inhibitor of the β-catenin/TCF4 complex, FH535...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28667416/satb2-suppresses-non-small-cell-lung-cancer-invasiveness-by-g9a
#15
Yi-Nan Ma, Hai-Yan Zhang, Liang-Ru Fei, Mei-Yu Zhang, Cong-Cong Wang, Yuan Luo, Yu-Chen Han
Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor, which plays an important role in transcriptional regulation and chromatin recombinant by combining with matrix attachment regions. More evidence shows that SATB2 is involved in progression of breast cancer, head and neck squamous cell carcinomas and osteosarcoma. However, the role of SATB2 in cancer initiation and progression is still not well understood. Our study identified that decreased expression of SATB2 was correlated with tumor progression and poor prognosis in non-small cell lung cancer (NSCLC) patients...
June 30, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28667355/visfatin-mediates-doxorubicin-resistance-in-human-colorectal-cancer-cells-via-up-regulation-of-multidrug-resistance-1-mdr1
#16
Xiaofei Yan, Jian Zhao, Rui Zhang
Colorectal cancer (CRC) is one of the prevalent and deadly cancers worldwide. Chemotherapy resistance is one of the most challenging problems for CRC and other cancer treatments. Recent studies indicated that increasing levels of visfatin are correlated with worse clinical prognosis of CRC patients, while the effects and mechanisms of visfatin on progression of CRC remain unclear. Our present study established doxorubicin (Dox)-resistant CRC HCT-116 and SW480 cells (named HCT-116 Dox/R and SW480 Dox/R). The expression of visfatin, while not IL-6, IL-8, or TGF-β, in CRC Dox-resistant cells was significantly greater than that in their parental cells, while knockdown of visfatin by its specific siRNAs can elevate Dox sensitivity of CRC-resistant cells...
June 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28667302/e2f1-regulated-long-non-coding-rna-rad51-as1-promotes-cell-cycle-progression-inhibits-apoptosis-and-predicts-poor-prognosis-in-epithelial-ovarian-cancer
#17
Xiaodan Zhang, Guoping Liu, Junjun Qiu, Ning Zhang, Jingxin Ding, Keqin Hua
Long non-coding RNA RAD51 antisense RNA 1 (RAD51-AS1, also known as TODRA) has been shown to be down-regulated by E2F1, a key cell cycle and apoptosis regulator, in breast cancer. Little is known regarding the role of RAD51-AS1 in disease. Here, we investigate the role of RAD51-AS1 in epithelial ovarian cancer (EOC). Using luciferase reporter and chromatin immunoprecipitation experiments, we verified RAD51-AS1 as a target of E2F1 under negative regulation in EOC. We then examined RAD51-AS1 expression in EOC samples using in situ hybridization (ISH)...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28667082/new-hif2a-inhibitors-implications-for-pheochromocytomas-and-paragangliomas
#18
Rodrigo Almeida Toledo
Two recent independent studies published in Nature show robust responses of clear cell renal cell carcinoma (ccRCC) cell lines, preclinical ccRCC xenograft models and, remarkably, a patient with progressive ccRCC despite receiving multiple lines of treatment, to the long-awaited, recently developed inhibitors of hypoxia-inducible factor 2-alpha (HIF2α). This Commentary is based on the recognition of similar molecular drivers in ccRCC and the endocrine neoplasias pheochromocytomas and paragangliomas (PPGLs), ultimately leading to stabilization of HIFs...
June 30, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28666371/the-identification-of-fancd2-dna-binding-domains-reveals-nuclear-localization-sequences
#19
Joshi Niraj, Marie-Christine Caron, Karine Drapeau, Stéphanie Bérubé, Laure Guitton-Sert, Yan Coulombe, Anthony M Couturier, Jean-Yves Masson
Fanconi anemia (FA) is a recessive genetic disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. The FA pathway consists of at least 21 FANC genes (FANCA-FANCV), and the encoded protein products interact in a common cellular pathway to gain resistance against DNA interstrand crosslinks. After DNA damage, FANCD2 is monoubiquitinated and accumulates on chromatin. FANCD2 plays a central role in the FA pathway, using yet unidentified DNA binding regions...
June 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28665819/targeting-ezh2-in-cancer-therapy
#20
Makoto Yamagishi, Kaoru Uchimaru
PURPOSE OF REVIEW: The present review introduces recent outstanding progress pertaining to Enhancer of zeste homolog 2 (EZH2), especially regarding its mode of action as a master regulator of chromatin, and provides molecular-based evidence for targeting EZH2 in cancer therapy. We discuss the active development of small molecules targeting the enzymatic activity of EZH2/polycomb repressive complex 2 (PRC2). RECENT FINDINGS: Genetic, transcriptional, and posttranscriptional dysregulation of EZH2 is frequently observed in many cancer types...
July 13, 2017: Current Opinion in Oncology
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