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Epigenetic and cancer

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https://www.readbyqxmd.com/read/28088786/ezh2-inhibition-suppresses-endometrial-cancer-progression-via-mir-361-twist-axis
#1
Kei Ihira, Peixin Dong, Ying Xiong, Hidemichi Watari, Yosuke Konno, Sharon Jb Hanley, Masayuki Noguchi, Noriyuki Hirata, Futoshi Suizu, Takahiro Yamada, Masataka Kudo, Noriaki Sakuragi
EZH2 inhibition and reactivation of tumor suppressor microRNAs (miRNAs) represent attractive anti-cancer therapeutic strategies. We found that EZH2-suppressed let 7b and miR-361, two likely tumor suppressors, inhibited endometrial cancer (EC) cell proliferation and invasion, and abrogated cancer stem cell-like properties. In EC cells, EZH2 induced and functioned together with YY1 to epigenetically suppress miR-361, which upregulated Twist, a direct target of miR-361. Treating EC cells with GSK343, a specific EZH2 inhibitor, mimicked the effects of siRNA-mediated EZH2 knockdown, upregulating miR-361 and downregulating Twist expression...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088687/whole-genome-dna-methylation-profiling-identifies-epigenetic-signatures-of-uterine-carcinosarcoma
#2
Jing Li, Xiaoyun Xing, Daofeng Li, Bo Zhang, David G Mutch, Ian S Hagemann, Ting Wang
Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous components of three UCS samples separated by laser capture microdissection and compared DNA methylomes of UCS with those of normal endometrium as well as methylomes derived from endometrioid carcinoma, serous endometrial carcinoma, and endometrial stromal sarcoma...
January 12, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28088579/the-microrna-449-family-inhibits-tgf-%C3%AE-mediated-liver-cancer-cell-migration-by-targeting-sox4
#3
Maria Sandbothe, Reena Buurman, Nicole Reich, Luisa Greiwe, Beate Vajen, Engin Gürlevik, Vera Schäffer, Marlies Eilers, Florian Kühnel, Alejandro Vaquero, Thomas Longerich, Stephanie Roessler, Peter Schirmacher, Michael P Manns, Thomas Illig, Brigitte Schlegelberger, Britta Skawran
BACKGROUND & AIMS: Modulation of microRNA expression is considered for treatment of hepatocellular carcinoma (HCC). Therefore, we characterized the epigenetically regulated microRNA-449 family (miR-449a, miR-449b, miR-449c) with regards to its functional effects and target genes in HCC. METHODS: After transfection of miR-449a, miR-449b, and/or miR-449c, tumor-relevant functional effects were analyzed using in vitro assays and a xenograft mouse model. Binding specificities, target genes, and regulated pathways of each microRNA were identified by microarray analyses...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28081549/microrna-promoter-methylation-a-new-tool-for-accurate-detection-of-urothelial-carcinoma
#4
Nuno André Padrão, Sara Monteiro-Reis, Jorge Torres-Ferreira, Luís Antunes, Luís Leça, Diana Montezuma, João Ramalho-Carvalho, Paula C Dias, Paula Monteiro, Jorge Oliveira, Rui Henrique, Carmen Jerónimo
BACKGROUND: Urothelial carcinoma (UC) is the most common cancer affecting the urinary system, worldwide. Lack of accurate early detection tools entails delayed diagnosis, precluding more efficient and timely treatment. In a previous study, we found that miR-129-2 and miR-663a were differentially methylated in UC compared with other genitourinary tract malignancies. Here, we evaluated the diagnostic performance of those microRNAs in urine. METHODS: Promoter methylation levels of miR-129-2 and miR-663a were assessed, using real-time quantitative methylation-specific PCR, in UC tissue samples (using normal urothelium as control) and, subsequently, in urine samples from UC and other genitourinary malignancies...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28079712/a-comprehensive-review-of-genomics-and-noncoding-rna-in-gliomas
#5
Ahmed Hassan, Jennifer Mosley, Sanjay Singh, Pascal Olivier Zinn
Glioblastoma (GBM) is the most malignant primary adult brain tumor. In spite of our greater understanding of the biology of GBMs, clinical outcome of GBM patients remains poor, as their median survival with best available treatment is 12 to 18 months. Recent efforts of The Cancer Genome Atlas (TCGA) have subgrouped patients into 4 molecular/transcriptional subgroups: proneural, neural, classical, and mesenchymal. Continuing efforts are underway to provide a comprehensive map of the heterogeneous makeup of GBM to include noncoding transcripts, genetic mutations, and their associations to clinical outcome...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28079155/dietary-phytochemical-peitc-restricts-tumor-development-via-modulation-of-epigenetic-writers-and-erasers
#6
Jung Eun Park, Yang Sun, Sai Kiang Lim, James P Tam, Matthijs Dekker, Hong Chen, Siu Kwan Sze
Dietary intake of bioactive phytochemicals including the cruciferous vegetable derivative phenethyl isothiocyanate (PEITC) can reduce risk of human cancers, but possible epigenetic mechanisms of these effects are yet unknown. We therefore sought to identify the molecular basis of PEITC-mediated epigenetic tumor restriction. Colon cancer cells treated with low-dose PEITC for >1 month exhibited stable alterations in expression profile of epigenetic writers/erasers and chromatin-binding of histone deacetylases (HDACs) and Polycomb-group (PcG) proteins...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079011/molecular-mechanisms-of-anticancer-effects-of-phytoestrogens-in-breast-cancer
#7
Chia-Jung Hsieh, Ya-Ling Hsu, Ya-Fang Huang, Eing-Mei Tsai
Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#8
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28078999/hdacs-and-hdac-inhibitors-in-urothelial-carcinoma-perspectives-for-an-antineoplastic-treatment
#9
Maria Pinkerneil, Michèle J Hoffmann, Wolfgang A Schulz, Günter Niegisch
Histone deacetylases (HDACs) influence diverse cellular processes and may contribute to tumor development and progression by multiple mechanisms. Class I HDACs are often overexpressed in cancers contributing to a genome-wide epigenetic state permitting increased proliferation, and diminished apoptosis and cell differentiation. Class IIA and IIB isoenzymes may likewise contribute to tumorigenesis as components of specific intranuclear repressor complexes or regulators of posttranslational protein modifications...
January 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#10
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28078123/diminished-expression-of-mgmt-rassf1a-genes-in-gastric-cancer-in-ethnic-population-of-kashmir
#11
Arif Akbar Bhat, Hilal Ahmad Wani, Ajaz Ahmad Waza, Rawoof Ahmad Malik, Akbar Masood, Showkat Jeelani, Showkat Kadla, Sabhiya Majid
BACKGROUND: Cancer initiation and progression are accompanied by profound changes in DNA. DNA methylation that was the first epigenetic alterations identified in cancer. DNA hypermethylation at promoter sites is closely associated with down regulation of protein and as major participant in the development and progression of series of human tumors. Therefore we hypothesized that promoter hypermethylation of RASSF1A & MGMT gene could influence susceptibility to gastric cancer (GC) as well, and we conducted this study to test the hypothesis in Kashmiri population...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28077801/human-papillomavirus-type-16-e6-suppresses-microrna-23b-expression-in-human-cervical-cancer-cells-through-dna-methylation-of-the-host-gene-c9orf3
#12
Chi Lam Au Yeung, Tsun Yee Tsang, Pak Lun Yau, Tim Tak Kwok
Oncogenic protein E6 of human papillomavirus type 16 (HPV-16) is believed to involve in the aberrant methylation in cervical cancer as it upregulates DNA methyltransferase 1 (DNMT1) through tumor suppressor p53. In addition, DNA demethylating agent induces the expression of one of the HPV-16 E6 regulated microRNAs (miRs), miR-23b, in human cervical carcinoma SiHa cells. Thus, the importance of DNA methylation and miR-23b in HPV-16 E6 associated cervical cancer development is investigated. In the present study, however, it is found that miR-23b is not embedded in any typical CpG island...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077797/repression-of-fyn-related-kinase-in-breast-cancer-cells-is-associated-with-promoter-site-specific-cpg-methylation
#13
Edward T Bagu, Sayem Miah, Chenlu Dai, Travis Spriggs, Yetunde Ogunbolude, Erika Beaton, Michelle Sanders, Raghuveera K Goel, Keith Bonham, Kiven E Lukong
The triple-negative breast cancer subtype is highly aggressive and has no defined therapeutic target. Fyn-related kinase (FRK) is a non-receptor tyrosine kinase, reported to be downregulated in breast cancer and gliomas, where it is suggested to have tumor suppressor activity. We examined the expression profile of FRK in a panel of 40 breast cancer cells representing all the major subtypes, as well as in 4 non-malignant mammary epithelial cell lines. We found that FRK expression was significantly repressed in a proportion of basal B breast cancer cell lines...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077379/effects-of-supplementation-with-nondigestible-carbohydrates-on-fecal-calprotectin-and-on-epigenetic-regulation-of-sfrp1-expression-in-the-large-bowel-mucosa-of-healthy-individuals
#14
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Idoia Ibero-Baraibar, Wing C Leung, Seamus Kelly, D Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
BACKGROUND: Hyperactive Wnt signaling is frequently observed in colorectal cancer. Higher intakes of dietary fiber [nondigestible carbohydrates (NDCs)] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway. OBJECTIVES: We investigated the effects of supplementing healthy individuals with 2 NDCs [resistant starch (RS) and polydextrose] on fecal calprotectin concentrations and Wnt pathway-related gene expression...
January 11, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28077137/aberrant-methylation-of-dact1-and-dact2-are-associated-with-tumor-progression-and-poor-prognosis-in-esophageal-squamous-cell-carcinoma
#15
Yan-Li Guo, Bao-En Shan, Wei Guo, Zhi-Ming Dong, Zhen Zhou, Su-Peng Shen, Xin Guo, Jia Liang, Gang Kuang
BACKGROUND: The DACT (Dishevelled-associated antagonist of β-catenin) family of scaffold proteins may play important roles in tumorigenesis. However, the epigenetic changes of DACT1, 2, 3 and their effect on esophageal squamous cell carcinoma (ESCC) have not been investigated so far. The aim of this study was to investigate the promoter methylation and expression of DACT family, in order to elucidate more information on the role of DACT with regard to the progression and prognosis of ESCC...
January 11, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28076901/nuclear-factor-one-transcription-factors-as-epigenetic-regulators-in-cancer
#16
REVIEW
Mitchell Fane, Lachlan Harris, Aaron G Smith, Michael Piper
Tumour heterogeneity poses a distinct obstacle to therapeutic intervention. While the initiation of tumours across various physiological systems is frequently associated with signature mutations in genes that drive proliferation and bypass senescence, increasing evidence suggests that tumour progression and clonal diversity is driven at an epigenetic level. The tumour microenvironment plays a key role in driving diversity as cells adapt to demands during tumour growth, and is thought to drive certain subpopulations back to a stem cell-like state...
January 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28076791/mll-af4-spreading-identifies-binding-sites-that-are-distinct-from-super-enhancers-and-that-govern-sensitivity-to-dot1l-inhibition-in-leukemia
#17
Jon Kerry, Laura Godfrey, Emmanouela Repapi, Marta Tapia, Neil P Blackledge, Helen Ma, Erica Ballabio, Sorcha O'Byrne, Frida Ponthan, Olaf Heidenreich, Anindita Roy, Irene Roberts, Marina Konopleva, Robert J Klose, Huimin Geng, Thomas A Milne
Understanding the underlying molecular mechanisms of defined cancers is crucial for effective personalized therapies. Translocations of the mixed-lineage leukemia (MLL) gene produce fusion proteins such as MLL-AF4 that disrupt epigenetic pathways and cause poor-prognosis leukemias. Here, we find that at a subset of gene targets, MLL-AF4 binding spreads into the gene body and is associated with the spreading of Menin binding, increased transcription, increased H3K79 methylation (H3K79me2/3), a disruption of normal H3K36me3 patterns, and unmethylated CpG regions in the gene body...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076698/emerging-role-of-setdb1-as-a-therapeutic-target
#18
Archana Venkataramana Karanth, Radhika Radha Maniswami, Seema Prashanth, Hemalatha Govindaraj, Ramya Padmavathy, Sooriya Kumar Jegatheesan, Ramesh Mullangi, Sriram Rajagopal
Epigenetic changes lead to aberrant gene expression in cancer. SETDB1, a histone lysine methyltransferase plays an important role in methylation and gene silencing. Aberrant histone methylation at H3K9 by SETDB1 promotes silencing of tumor suppressor genes and thus contributes to carcinogenesis. Recent studies indicate that SETDB1 is abnormally expressed in various human cancer conditions which contributed to enhanced tumor growth and metastasis. Hence, SETDB1 appears to be a promising epigenetic target for therapeutic intervention...
January 11, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#19
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
January 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28074387/epigenetic-sampling-effects-nephrectomy-modifies-the-clear-cell-renal-cell-cancer-methylome
#20
Christophe Van Neste, Alexander Laird, Fiach O'Mahony, Wim Van Criekinge, Dieter Deforce, Filip Van Nieuwerburgh, Thomas Powles, David J Harrison, Grant D Stewart, Tim De Meyer
PURPOSE: Currently, it is unclear to what extent sampling procedures affect the epigenome. Here, this phenomenon was evaluated by studying the impact of artery ligation on DNA methylation in clear cell renal cancer. METHODS: DNA methylation profiles between vascularised tumour biopsy samples and devascularised nephrectomy samples from two individuals were compared. The relevance of significantly altered methylation profiles was validated in an independent clinical trial cohort...
January 10, 2017: Cellular Oncology (Dordrecht)
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