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https://www.readbyqxmd.com/read/28812986/epigenome-aberrations-emerging-driving-factors-of-the-clear-cell-renal-cell-carcinoma
#1
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/28811977/epigenetic-regulation-of-the-extrinsic-oncosuppressor-ptx3-gene-in-inflammation-and-cancer
#2
Marcello Rubino, Paolo Kunderfranco, Gianluca Basso, Carolina Magdalen Greco, Fabio Pasqualini, Simone Serio, Massimo Roncalli, Luigi Laghi, Alberto Mantovani, Roberto Papait, Cecilia Garlanda
PTX3 is a component of the humoral arm of innate immunity and an extrinsic oncosuppressor gene taming tumor-promoting inflammation. Here, we show that two enhancers differently regulate PTX3 expression: enhancer 1, located 230 kb upstream of PTX3 promoter, mediated the action of inflammatory transcription factors; and enhancer 2, encompassing PTX3 second exon, was implicated in pre-initiation complex assembly. Polycomb repressive complex 2 silenced these regulatory elements and the promoter in basal condition...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#3
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28809126/comprehensive-epigenetic-analysis-of-the-signature-genes-in-lung-adenocarcinoma
#4
Yunfeng Zhang, Weidong Zhao, Jia Zhang
AIM: This study aimed to explore the epigenetic modifications of signature genes in lung adenocarcinoma. MATERIALS & METHODS: The data of miRNA expression, mRNA expression and DNA methylation were downloaded from The Cancer Genome Atlas. Differential analysis was performed, followed by correlation analysis of miRNA-mRNA and DNA methylation-mRNA. RESULTS: A total of 14 significant inverse correlations between gene expression and DNA methylation were identified, the expressions of which were selected for further validation via GSE27262, displaying similar pattern with that of the integrated analysis...
August 15, 2017: Epigenomics
https://www.readbyqxmd.com/read/28807942/nuclear-fak-and-runx1-cooperate-to-regulate-igfbp3-cell-cycle-progression-and-tumor-growth
#5
Marta Canel, Adam Byron, Andrew H Sims, Jessy Cartier, Hitesh Patel, Margaret C Frame, Valerie G Brunton, Bryan Serrels, Alan Serrels
Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1 regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through post-translational modification...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28807688/hypochlorous-acid-induced-structural-and-conformational-modifications-in-human-dna-a-multi-spectroscopic-study
#6
Irfan Qadir Tantry, Sana Waris, Safia Habib, Rizwan Hasan Khan, Riaz Mahmood, Asif Ali
Hypochlorous acid (HOCl) is generated by activated phagocytes at the site of inflammation. Exposure of DNA to HOCl results in base and nucleotide modifications causing DNA damage, which is one of the leading causes of various pathological conditions including carcinogenesis. In the present work, various biophysical techniques were used to study HOCl induced structural and conformational changes in human placental DNA. The HOCl modified DNA showed hyperchromicity, reduced fluorescence and decrease in melting temperature...
August 11, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28807546/epigenetic-drivers-of-tumourigenesis-and-cancer-metastasis
#7
REVIEW
Aniruddha Chatterjee, Euan J Rodger, Michael R Eccles
Since the completion of the first human genome sequence and the advent of next generation sequencing technologies, remarkable progress has been made in understanding the genetic basis of cancer. These studies have mainly defined genetic changes as either causal, providing a selective advantage to the cancer cell (a driver mutation) or consequential with no selective advantage (not directly causal, a passenger mutation). A vast unresolved question is how a primary cancer cell becomes metastatic and what are the molecular events that underpin this process...
August 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28807232/ovarian-cancer-novel-molecular-aspects-for-clinical-assessment
#8
REVIEW
Raffaele Palmirotta, Erica Silvestris, Stella D'Oronzo, Angela Cardascia, Franco Silvestris
Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28806761/transcriptome-analysis-of-pdgfr%C3%AE-cells-identifies-t-type-ca2-channel-cacna1g-as-a-new-pathological-marker-for-pdgfr%C3%AE-cell-hyperplasia
#9
Se Eun Ha, Moon Young Lee, Masaaki Kurahashi, Lai Wei, Brian G Jorgensen, Chanjae Park, Paul J Park, Doug Redelman, Kent C Sasse, Laren S Becker, Kenton M Sanders, Seungil Ro
Platelet-derived growth factor receptor alpha (PDGFRα)+ cells are distributed into distinct morphological groups within the serosal, muscular, and submucosal layers as well as the myenteric and deep muscular plexi. PDGFRα+ cells directly interact with interstitial cells of Cajal (ICC) and smooth muscle cells (SMC) in gastrointestinal smooth muscle tissue. These three cell types, SMC, ICC, and PDGFRα+ cells (SIP cells), form an electrical syncytium, which dynamically regulates gastrointestinal motility. We have previously reported the transcriptomes of SMC and ICC...
2017: PloS One
https://www.readbyqxmd.com/read/28806395/rad6-promotes-dna-repair-and-stem-cell-signaling-in-ovarian-cancer-and-is-a-promising-therapeutic-target-to-prevent-and-treat-acquired-chemoresistance
#10
R R Somasagara, S M Spencer, K Tripathi, D W Clark, C Mani, L Madeira da Silva, J Scalici, H Kothayer, A D Westwell, R P Rocconi, K Palle
Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28805986/histiocytic-sarcoma-new-insights-into-fna-cytomorphology-and-molecular-characteristics
#11
Yin P Hung, Scott B Lovitch, Xiaohua Qian
BACKGROUND: Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic features of histiocytes. Molecular characteristics of HS and fine-needle aspiration (FNA) criteria for its diagnosis have not been established. METHODS: A case series of HS in 8 FNA samples from 6 patients was reviewed along with histopathologic and clinical data. Immunohistochemistry was performed on cell blocks (3 cases), core biopsies (5 cases), and surgical specimens (4 cases)...
August 2017: Cancer
https://www.readbyqxmd.com/read/28805496/natural-antisense-transcripts-drive-a-regulatory-cascade-controlling-c-myc-transcription
#12
Sara Napoli, Valentina Piccinelli, Sarah Mapelli, Giuseppina Pisignano, Carlo V Catapano
Cis-natural antisense transcripts (cis-NATs) are long noncoding RNAs transcribed from the opposite strand and overlapping coding and noncoding genes on the sense strand. cis-NATs are widely present in the human genome and can be involved in multiple mechanisms of gene regulation. Here, we describe the presence of cis-NATs in the 3' distal region of the c-MYC locus and investigate their impact on transcriptional regulation of this key oncogene in human cancers. We found that cis-NATs are produced as consequence of the activation of cryptic transcription initiation sites in the 3' distal region downstream of the c-MYC 3'UTR...
August 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28804688/pivotal-regulators-of-tissue-homeostasis-and-cancer-macrophages
#13
REVIEW
Yulei Chen, Xiaobo Zhang
Macrophages are an essential component of innate immunity and play a vital role in inflammation and host defense. Based on immunological responses, the macrophages are classified into "activated" macrophage (M1 macrophages) participating in the responses of type I helper T (Th1) cells to pathogens and "alternatively activated" macrophages (M2 macrophages) in response to interleukin (IL)-4 and IL-13. In this review, we discuss the origin, classification and function of macrophages. We also discuss the mechanisms underlying polarization of different macrophage subtypes, including transcriptional, epigenetic and post-transcriptional regulation...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#14
Emilie Evanno, Julie Godet, Nathalie Piccirilli, Joëlle Guilhot, Serge Milin, Jean Marc Gombert, Benoit Fouchaq, Joëlle Roche
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#15
REVIEW
Zachary Benson, Saeed H Manjili, Mehran Habibi, Georgi Guruli, Amir A Toor, Kyle K Payne, Masoud H Manjili
Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy...
August 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28802146/epigenetic-manipulation-of-host-chromatin-by-kaposi-sarcoma-associated-herpesvirus-a-tumor-promoting-factor
#16
REVIEW
Thomas Günther, Adam Grundhoff
Molecular and epidemiological evidence links Kaposi sarcoma-associated herpesvirus (KSHV) to a number of malignancies of endothelial or B cell origin. As for most virus-associated cancers, however, the tumor initiating and promoting events remain poorly understood. Given the emerging role of epigenetic alterations as drivers of human cancers, an interesting (and as of yet under-explored) hypothesis is that viral manipulation of host cell chromatin may contribute to the pathogenesis of KSHV-associated tumors...
August 9, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28801683/regulation-of-tumour-related-genes-by-dynamic-epigenetic-alteration-at-enhancer-regions-in-gastric-epithelial-cells-infected-by-epstein-barr-virus
#17
Atsushi Okabe, Sayaka Funata, Keisuke Matsusaka, Hiroe Namba, Masaki Fukuyo, Bahityar Rahmutulla, Motohiko Oshima, Atsushi Iwama, Masashi Fukayama, Atsushi Kaneda
Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. We analysed epigenetic alterations induced by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800922/inhibition-of-h3k4-demethylation-induces-autophagy-in-cancer-cell-lines
#18
Zhen Wang, Qiao-Yun Long, Lin Chen, Jia-Dong Fan, Zhao-Ning Wang, Lian-Yun Li, Min Wu
Epigenetic factors and related small molecules have emerged to be strongly involved in autophagy process. Here we report that 2-PCPA and GSK-LSD1, two inhibitors of histone H3K4 demethylase KDM1A/LSD1, induce autophagy in multiple mammalian cell lines. The two small molecules induce accumulation of LC3II, formation of autophagosome and autolysosome, and SQSTM1/p62 degradation. 2-PCPA treatment inhibits cell proliferation through cell cycle arrest but does not inducing cell death. Exogenous expression of KDM1A/LSD1 impaired the autophagic phenotypes triggered by 2-PCPA...
August 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28800870/recent-advances-in-her2-positive-breast-cancer-epigenetics-susceptibility-and-therapeutic-strategies
#19
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/28800814/phthalates-impact-human-health-epidemiological-evidences-and-plausible-mechanism-of-action
#20
REVIEW
Sailas Benjamin, Eiji Masai, Naofumi Kamimura, Kenji Takahashi, Robin C Anderson, Panichikkal Abdul Faisal
Disregarding the rising alarm on the hazardous nature of various phthalates and their metabolites, ruthless usage of phthalates as plasticizer in plastics and as additives in innumerable consumer products continues due low their cost, attractive properties, and lack of suitable alternatives. Globally, in silico computational, in vitro mechanistic, in vivo preclinical and limited clinical or epidemiological human studies showed that over a dozen phthalates and their metabolites ingested passively by man from the general environment, foods, drinks, breathing air, and routine household products cause various dysfunctions...
October 15, 2017: Journal of Hazardous Materials
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