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https://www.readbyqxmd.com/read/29334683/epigenetic-silencing-of-the-mlh1-promoter-in-relation-to-the-development-of-gastric-cancer-and-its-use-as-a-biomarker-for-patients-with-microsatellite-instability-a-systematic-analysis
#1
Guimei Hu, Lijun Qin, Xinjun Zhang, Guoliang Ye, Tao Huang
BACKGROUND/AIMS: Human mutL homolog 1 (MLH1) promoter methylation was reported in gastric cancer (GC). This study determined the clinicopathological, prognostic, and diagnostic effects of MLH1 promoter methylation in GC. METHODS: The combined odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area under the curve (AUC) were analyzed. RESULTS: A total of 4654 GC patients and 3669 non-malignant controls were identified in this systematic analysis...
January 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29333921/targeting-brd4-proteins-suppresses-the-growth-of-nsclc-through-downregulation-of-eif4e-expression
#2
Zhongyuan Gao, Ting Yuan, Xiao Zhou, Ping Ni, Geng Sun, Ping Li, Zhixiang Cheng, Xuerong Wang
Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain and extraterminal domain (BET) proteins act as epigenome readers for gene transcriptional regulation. Among BET family members, BRD4 was well studied, but for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E regulates gene translation and has been proved to play an important role in the progression of lung cancer. In this study, we first confirmed that BET inhibitors JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated eIF4E expression...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333422/epigenetic-inactivation-of-runx3-in-colorectal-cancer
#3
Eung Jin Shin, Han Jo Kim, Myoung Won Son, Tae Sung Ahn, Hyun Yong Lee, Dae Ro Lim, Sang Byung Bae, Seob Jeon, Hyungjoo Kim, Dongjun Jeong, Moon Soo Lee, Dong-Sun Kim, Jeong Se Noh, Moo-Jun Baek
Purpose: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. Methods: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study...
January 2018: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/29332326/carcinogenic-potential-of-antitumor-therapies-is-the-risk-predictable
#4
Ivanka Nenova, Janet Grudeva-Popova
The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331887/idh1r132h-promotes-malignant-transformation-of-benign-prostatic-epithelium-by-dysregulating-micrornas-involvement-of-igf1r-akt-stat3-signaling-pathway
#5
Lili Zhang, Mei Qi, Tingting Feng, Jing Hu, Lin Wang, Xinjun Li, Wei Gao, Hui Liu, Meng Jiao, Zhen Wu, Xinnuo Bai, Yifan Bie, Long Liu, Bo Han
Risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer (PCa). Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. Mutant IDH1 has been identified in various human malignancies, and IDH1R132H constituted the vast majority of mutational events of IDH1. Most recent studies suggested that IDH1 mutations define a methylator subtype in PCa...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331675/module-analysis-captures-pancancer-genetically-and-epigenetically-deregulated-cancer-driver-genes-for-smoking-and-antiviral-response
#6
Magali Champion, Kevin Brennan, Tom Croonenborghs, Andrew J Gentles, Nathalie Pochet, Olivier Gevaert
The availability of increasing volumes of multi-omics profiles across many cancers promises to improve our understanding of the regulatory mechanisms underlying cancer. The main challenge is to integrate these multiple levels of omics profiles and especially to analyze them across many cancers. Here we present AMARETTO, an algorithm that addresses both challenges in three steps. First, AMARETTO identifies potential cancer driver genes through integration of copy number, DNA methylation and gene expression data...
December 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29331027/mir-137-functions-as-a-tumor-suppressor-in-pancreatic-cancer-by-targeting-mrgbp
#7
Feng Ding, Shuang Zhang, Shaoyang Gao, Jian Shang, Yanxia Li, Ning Cui, Qiu Zhao
miRNAs are small noncoding RNAs that act as critical epigenetic regulators in tumor carcinogenesis. In this study, our data showed that miR-137 was significantly downregulated in 58 pairs of human pancreatic cancer (PanCa) tissues and PanCa cell lines. Furthermore, the deregulated miR-137 was correlated with increased tumor size, higher TNM stage, and worse prognosis in pancreatic cancer. Functional studies demonstrated that overexpression of miR-137 dramatically suppressed cell proliferation and induced cell apoptosis in vitro...
January 13, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29330943/epigenetic-markers-in-circulating-cell-free-dna-as-prognostic-markers-for-survival-of-castration-resistant-prostate-cancer-patients
#8
Rianne J Hendriks, Siebren Dijkstra, Frank P Smit, Johan Vandersmissen, Hendrik Van de Voorde, Peter F A Mulders, Inge M van Oort, Wim Van Criekinge, Jack A Schalken
BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. METHODS: In this prospective study, patients were included before starting new treatment after developing CRPC...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330773/mechanistic-regulation-of-epithelial-to-mesenchymal-transition-through-ras-signaling-pathway-and-therapeutic-implications-in-human-cancer
#9
REVIEW
Kiran Tripathi, Minal Garg
RAS effector signaling instead of being simple, unidirectional and linear cascade, is actually recognized as highly complex and dynamic signaling network. RAF-MEK-ERK cascade, being at the center of complex signaling network, links to multiple scaffold proteins through feed forward and feedback mechanisms and dynamically regulate tumor initiation and progression. Three isoforms of Ras harbor mutations in a cell and tissue specific manner. Besides mutations, their epigenetic silencing also attributes them to exhibit oncogenic activities...
January 12, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29330379/identification-of-shared-genetic-variants-between-schizophrenia-and-lung-cancer
#10
Verena Zuber, Erik G Jönsson, Oleksandr Frei, Aree Witoelar, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Yunpeng Wang, Srdjan Djurovic, Olav B Smeland, Ingrid Dieset, Ayman H Fanous, Rahul S Desikan, Sébastien Küry, Stéphane Bézieau, Anders M Dale, Ian G Mills, Ole A Andreassen
Epidemiology studies suggest associations between schizophrenia and cancer. However, the underlying genetic mechanisms are not well understood, and difficult to identify from epidemiological data. We investigated if there is a shared genetic architecture between schizophrenia and cancer, with the aim to identify specific overlapping genetic loci. First, we performed genome-wide enrichment analysis and second, we analyzed specific loci jointly associated with schizophrenia and cancer by the conjunction false discovery rate...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330295/epigenetic-reprogramming-of-pericentromeric-satellite-dna-in-premalignant-and-malignant-lesions
#11
Nadine H Brueckmann, Christina B Pedersen, Henrik J Ditzel, Morten F Gjerstorff
Repression of repetitive DNA is important for maintaining genomic stability, but is often perturbed in cancer. For instance, the megabase satellite domain at chromosome 1q12 is a common site of genetic rearrangements, such as translocations and deletions. Polycomb-group (PcG) proteins can be observed as large subnuclear domains called polycomb bodies, the composition and cellular function of which has remained elusive. This study, demonstrates that polycomb bodies are canonical subunits of the multiprotein polycomb repressive complex 1 (PRC1) deposited on 1q12 pericentromeric satellite DNA, which are normally maintained as constitutive heterochromatin by other mechanisms...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330288/epigenetically-regulated-chromosome-14q32-mirna-cluster-induces-metastasis-and-predicts-poor-prognosis-in-lung-adenocarcinoma-patients
#12
Margarita Gonzalez-Vallinas, Manuel Rodriguez-Paredes, Marco Albrecht, Carsten Sticht, Damian Stichel, Julian Gutekunst, Adriana Pitea, Steffen Sass, Francisco J Sánchez-Rivera, Justo L Bermejo, Jennifer Schmitt, Carolina De La Torre, Arne Warth, Fabian Theis, Nikola Mueller, Norbert Gretz, Thomas Muley, Michael Meister, Darjus F Tschaharganeh, Peter Schirmacher, Franziska Matthäus, Kai Breuhahn
Most lung cancer deaths are related to metastases, which indicates the necessity of detecting and inhibiting tumor cell dissemination. Here, we aimed to identify microRNAs (miRNAs) involved in metastasis of lung adenocarcinoma as prognostic biomarkers and therapeutic targets. To that end, lymph node metastasis-associated miRNAs were identified in The Cancer Genome Atlas (TCGA) lung adenocarcinoma patient cohort (sequencing data; n=449) and subsequently validated by RT-qPCR in an independent clinical cohort (n=108)...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330282/population-dependent-intron-retention-and-dna-methylation-in-breast-cancer
#13
Dongwook Kim, Manu Shivakumar, Seonggyun Han, Michael S Sinclair, Youngji Lee, Yonglan Zheng, Olufunmilayo I Olopade, Dokyoon Kim, Younghee Lee
Regulation of gene expression by DNA methylation in gene promoter regions is well-studied; however, the effects of methylation in the gene body (exons and introns) on gene expression are comparatively understudied. Recently, hyper-methylation has been implicated in the inclusion of alternatively spliced exons; moreover, exon recognition can be enhanced by recruiting the methyl-CpG-binding protein (MeCP2) to hyper-methylated sites. This study examines if methylation status of an intron is correlated with how frequently the intron is retained during splicing using DNA methylation and RNA sequencing (RNA-seq) data from breast cancer tissue specimens in The Cancer Genome Atlas (TCGA)...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330202/high-risk-tp53-mutations-are-associated-with-extra-nodal-extension-ene-in-oral-cavity-squamous-cell-carcinoma-oscc
#14
Vlad C Sandulache, Chieko Michikawa, Pranav Kataria, Frederico O Gleber-Netto, Diana Bell, Sanchit Trivedi, Xiayu Rao, Jing Wang, Mei Zhao, Samar A Jasser, Jeffrey N Myers, Curtis R Pickering
PURPOSE:   Development of extra-nodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection. EXPERIMENTAL DESIGN: An institutional cohort (University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29329300/symmetric-dimeric-bisbenzimidazoles-dbp-n-reduce-methylation-of-rarb-and-pten-while-significantly-increase-methylation-of-rrna-genes-in-mcf-7-cancer-cells
#15
Svetlana V Kostyuk, Margarita A Kvasha, Daria A Khrabrova, Olga V Kirsanova, Elizaveta S Ershova, Elena M Malinovskaya, Natalia N Veiko, Alexander A Ivanov, Vasiliy S Koval, Alexei L Zhuze, Vadim H Tashlitsky, Pavel E Umriukhin, Sergey I Kutsev, Elizaveta S Gromova
BACKGROUND: Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n) are able to block DNA methyltransferase activities. It was also found that DBP(n) produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome...
2018: PloS One
https://www.readbyqxmd.com/read/29326345/microrna-452-exerts-growth-suppressive-activity-against-t-cell-acute-lymphoblastic-leukemia
#16
Haihao Wang, Qiannan Guo, Guizhi Zhu, Shuo Zhu, Peiwen Yang, Mingsheng Zhang
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer. Although microRNA (miR)-452 serves as a tumor suppressor in multiple solid tumors, its expression and function in hematological cancers including T-ALL is largely unknown. We measured the expression of miR-452 in 38 T-ALL and 22 normal lymph node samples by real-time PCR analysis. The methylation levels in the promoter of miR-452 were determined using MethyLight assay. The effects of miR-452 overexpression on proliferation, cell cycle distribution, and tumorigenesis were explored...
January 10, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29326042/keratin-13-gene-is-epigenetically-suppressed-during-transforming-growth-factor-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-a-human-keratinocyte-cell-line
#17
Mitsutoki Hatta, Yuki Miyake, Kunitoshi Uchida, Jun Yamazaki
Epithelial-mesenchymal transition (EMT) is a biological event in which epithelial cells lose their polarity and cell-cell adhesions and concomitantly acquire mesenchymal traits, and is thought to play an important role in pathological processes such as wound healing and cancer progression. In this study, we evaluated transforming growth factor (TGF)-β1-treated human keratinocyte HaCaT cells as an in vitro model of EMT. HaCaT cells were changed into an elongated fibroblast-like morphology, which is indicative of EMT in response to TGF-β1...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29325547/paracrine-and-epigenetic-control-of-caf-induced-metastasis-the-role-of-hotair-stimulated-by-tgf-%C3%A3-1-secretion
#18
Yu Ren, Huan-Huan Jia, Yi-Qi Xu, Xuan Zhou, Xiao-Hui Zhao, Yun-Fei Wang, Xin Song, Zhi-Yan Zhu, Ting Sun, Yan Dou, Wei-Ping Tian, Xiu-Lan Zhao, Chun-Sheng Kang, Mei Mei
BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines...
January 11, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29322419/analysis-of-dna-methylation-in-tissues-exposed-to-inflammation
#19
Naoko Hattori, Toshikazu Ushijima
Induction of aberrant DNA methylation is one of the most important mechanisms mediating the effect of inflammation on cancer development. Aberrant methylation of promoter CpG islands of tumor suppressor genes can silence their downstream genes, and that in cancer tissues is associated with prognosis or therapeutic effects. In addition, aberrant methylation can occur in tissues exposed to specific types of inflammation, producing a so-called "epigenetic field for cancerization," and its accumulation is correlated with cancer risk...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29322286/hyperglycemia-and-aberrant-o-glcnacylation-contributions-to-tumor-progression
#20
REVIEW
Andréia Vasconcelos-Dos-Santos, Rafaela Muniz de Queiroz, Bruno da Costa Rodrigues, Adriane R Todeschini, Wagner B Dias
A number of cancer types have shown an increased prevalence and a higher mortality rate in patients with hyperglycemic associated pathologies. Although the correlation between diabetes and cancer incidence has been increasingly reported, the underlying molecular mechanisms beyond this association are not yet fully understood. Recent studies have suggested that high glucose levels support tumor progression through multiple mechanisms that are hallmarks of cancer, including cell proliferation, resistance to apoptosis, increased cell migration and invasiveness, epigenetic regulation (hyperglycemic memory), resistance to chemotherapy and altered metabolism...
January 11, 2018: Journal of Bioenergetics and Biomembranes
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