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Epigenetic and cancer

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https://www.readbyqxmd.com/read/28749470/mir-181d-and-c-myc-mediated-inhibition-of-cry2-and-fbxl3-reprograms-metabolism-in-colorectal-cancer
#1
Xiaofeng Guo, Yuekun Zhu, Xinya Hong, Mukun Zhang, Xingfeng Qiu, Zhenfa Wang, Zhongquan Qi, Xuehui Hong
Colorectal cancer (CRC) is the second major cause of tumor-related deaths. MicroRNAs (miRNAs) have pivotal roles in CRC progression. Here, we describe the effect of miR-181d on CRC cell metabolism and underlying molecular mechanism. Our data firmly demonstrated that knockdown of miR-181d suppressed CRC cell proliferation, migration, and invasion by impairing glycolysis. Mechanistically, miR-181d stabilized c-myc through directly targeting the 3'-UTRs of CRY2 and FBXL3, which subsequently increased the glucose consumption and the lactate production...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28748501/a-step-by-step-microrna-guide-to-cancer-development-and-metastasis
#2
REVIEW
Georgios S Markopoulos, Eugenia Roupakia, Maria Tokamani, Evangelia Chavdoula, Maria Hatziapostolou, Christos Polytarchou, Kenneth B Marcu, Athanasios G Papavassiliou, Raphael Sandaltzopoulos, Evangelos Kolettas
BACKGROUND: Cancer is one of the leading causes of mortality. The neoplastic transformation of normal cells to cancer cells is caused by a progressive accumulation of genetic and epigenetic alterations in oncogenes, tumor suppressor genes and epigenetic regulators, providing cells with new properties, collectively known as the hallmarks of cancer. During the process of neoplastic transformation cells progressively acquire novel characteristics such as unlimited growth potential, increased motility and the ability to migrate and invade adjacent tissues, the ability to spread from the tumor of origin to distant sites, and increased resistance to various types of stresses, mostly attributed to the activation of genetic stress-response programs...
July 26, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28748258/ezh2-is-involved-in-silencing-of-wnt5a-during-epithelial-mesenchymal-transition-of-colon-cancer-cell-line
#3
Jianxin Tao, Liping Shi, Longchang Huang, Haoze Shi, Hang Chen, Yixin Wang, Tong Wang
PURPOSE: Transforming growth factor-β (TGF-β) induction of epithelial-mesenchymal transition (EMT) in SW480 was established as a system for studies of colon cancer metastasis. However, the epigenetic mechanisms underlying this process remain unknown. In mammal, polycomb repressive complex-2 (PRC2) is a highly conserved histone methyltransferase involved in epigenetic regulations. Enhancer of zeste Homolog 2 (EZH2) is the catalytic subunit of PRC2, which catalyzes methylation of lysine 27 of histone H3 (H3K27)...
July 26, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28748218/autophagy-regulated-by-mirnas-in-colorectal-cancer-progression-and-resistance
#4
Andrew Fesler, Hua Liu, Ning Wu, Fei Liu, Peixue Ling, Jingfang Ju
The catabolic process of autophagy is an essential cellular function that allows for the breakdown and recycling of cellular macromolecules. In recent years, the impact of epigenetic regulation of autophagy by non-coding microRNAs (miRNAs) has been recognized in human cancer. In colorectal cancer, Autophagy plays critical roles in cancer progression as well as resistance to chemotherapy, and recent evidence demonstrates that miRNAs are directly involved in mediating these functions. In this review, we will focus on the recent advancements in the field of miRNA regulation of autophagy in colorectal cancer...
2017: Cancer Translational Medicine
https://www.readbyqxmd.com/read/28748002/high-levels-of-circulating-folate-concentrations-are-associated-with-dna-methylation-of-tumor-suppressor-and-repair-genes-p16-mlh1-and-mgmt-in-elderly-chileans
#5
Hugo Sanchez, Mohammad B Hossain, Lydia Lera, Sandra Hirsch, Cecilia Albala, Ricardo Uauy, Karin Broberg, Ana M Ronco
BACKGROUND: Changes in DNA methylation, one of the most studied epigenetic mechanisms, are considered an initial marker for early cancer detection. We evaluated how availability of dietary factors (folates and vitamin B12) involved in one-carbon metabolism may contribute to DNA methylation changes of cancer-related genes in human subjects. METHODS: We studied, by pyrosequencing, the methylation of tumor suppressor gene p16, DNA repair genes MLH1 and MGMT, and the repetitive element LINE-1 (as a surrogate for global DNA methylation), in blood of elderly individuals (n = 249) who had been exposed to folic acid (FA) through FA-fortified wheat flour during the last 12 years...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28747748/the-epigenetic-landscape-of-promoter-genome-wide-analysis-in-breast-cancer
#6
Seher Karsli-Ceppioglu, Aslihan Dagdemir, Gaëlle Judes, André Lebert, Frédérique Penault-Llorca, Yves-Jean Bignon, Dominique Bernard-Gallon
Breast cancer is a heterogeneous disease due to its clinico-pathological features and response to therapy. The classification of breast tumors based on their hormone receptor status and pathologic features. Post-translational histone modifications come into prominence for regulation of gene expression in cancer pathogenesis. Here, we analyzed dysregulation of H3K9ac and H3K27me3-enriched subtype-specific genes using ChIP-on-chip assay in breast cancer tumors and matched normal tissue samples. Breast cancer tumors were classified according to St Gallen Consensus 2013...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747565/ctcf-promotes-epithelial-ovarian-cancer-metastasis-by-broadly-controlling-the-expression-of-metastasis-associated-genes
#7
Lintao Zhao, Yang Yang, Shigang Yin, Tao Yang, Jing Luo, Rongkai Xie, Haixia Long, Lubin Jiang, Bo Zhu
CCCTC-binding factor (CTCF) functions as both an oncogenic and a tumor suppressor, depending on the cancer type, through epigenetic regulation. Epigenetic regulation plays a key role in cancer metastasis. Our objective was to investigate whether CTCF plays a crucial role in epithelial ovarian cancer metastasis. First, we found that CTCF expression was increased in ovarian cancer tissues compared to non-tumor tissues. Increased expression of CTCF predicts poor prognosis of ovarian cancer patients. In addition, CTCF knockdown significantly inhibited the metastasis of ovarian cancer cells, although it had no effect on cell proliferation and tumor growth...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747541/obesity-a-serious-etiologic-factor-for-male-subfertility-in-modern-society
#8
Yue Liu, Zhide Ding
Obesity, defined as excessive accumulation of fat in adipose tissue, is a metabolic disorder resulting from behavioral, environmental and heritable causes. Such malfunction increases the risk of developing hypertension, diabetes, cardiovascular disease, respiratory problems, osteoarthritis and cancer. Meanwhile, the negative impact of obesity on male reproduction is gradually being recognized. According to clinical investigations and animal experiments, obesity is correlated with reductions in sperm concentration and motility, increases in sperm DNA damage and changes in reproductive hormonal levels...
July 26, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28747513/repression-of-bet-activity-sensitizes-homologous-recombination-proficient-cancers-to-parp-inhibition
#9
Lu Yang, Youyou Zhang, Weiwei Shan, Zhongyi Hu, Jiao Yuan, Jingjiang Pi, Yueying Wang, Lingling Fan, Zhaoqing Tang, Chunsheng Li, Xiaowen Hu, Janos L Tanyi, Yi Fan, Qihong Huang, Kathleen Montone, Chi V Dang, Lin Zhang
Strategies to enhance response to poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) in primary and acquired homologous recombination (HR)-proficient tumors would be a major advance in cancer care. We used a drug synergy screen that combined a PARPi, olaparib, with 20 well-characterized epigenetic drugs and identified bromodomain and extraterminal domain inhibitors (BETis; JQ1, I-BET762, and OTX015) as drugs that acted synergistically with olaparib in HR-proficient cancer cells. Functional assays demonstrated that repressed BET activity reduces HR and thus enhances PARPi-induced DNA damage in cancer cells...
July 26, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28744854/bok-displays-cell-death-independent-tumor-suppressor-activity-in-non-small-cell-lung-carcinoma
#10
Erika Moravcikova, Evzen Krepela, Vera S Donnenberg, Albert D Donnenberg, Kamila Benkova, Tatiana Rabachini, Yuniel Fernandez-Marrero, Daniel Bachmann, Thomas Kaufmann
Since the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is frequently deleted in certain human cancers, BOK is hypothesized to have a tumor suppressor function. In the present study, we analyzed primary non-small cell lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically treated patients. We show that BOK protein levels are significantly downregulated in NSCLC tumors as compared to lung tissues (P<0.001). In particular, we found BOK downregulation in NSCLC tumors of grades two (P=0...
July 26, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28743252/quantification-of-tumour-evolution-and-heterogeneity-via-bayesian-epiallele-detection
#11
James E Barrett, Andrew Feber, Javier Herrero, Miljana Tanic, Gareth A Wilson, Charles Swanton, Stephan Beck
BACKGROUND: Epigenetic heterogeneity within a tumour can play an important role in tumour evolution and the emergence of resistance to treatment. It is increasingly recognised that the study of DNA methylation (DNAm) patterns along the genome - so-called 'epialleles' - offers greater insight into epigenetic dynamics than conventional analyses which examine DNAm marks individually. RESULTS: We have developed a Bayesian model to infer which epialleles are present in multiple regions of the same tumour...
July 25, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28742980/disease-relevant-modifications-of-the-methylome-and-transcriptome-by-particulate-matter-pm2-5-from-biomass-combustion
#12
Katharina Heßelbach, Gwang-Jin Kim, Stephan Flemming, Thomas Häupl, Marc Bonin, Regina Dornhof, Stefan Günther, Irmgard Merfort, Matjaz Humar
Exposure to particulate matter (PM) is recognized as a major health hazard, but molecular responses are still insufficiently described. We analyzed the epigenetic impact of ambient PM2.5 from biomass combustion on the methylome of primary human bronchial epithelial BEAS-2B cells using the Illumina HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix HG-U133 Plus 2.0 Array. PM2.5 induced genome wide alterations of the DNA methylation pattern, including differentially methylated CpGs in the promoter region associated with CpG islands...
July 25, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28741490/in-vivo-rnai-screening-for-pancreatic-cancer-drivers-piloting-the-wdr5-myc-axis
#13
Günter Schneider, Dieter Saur
Pancreatic ductal adenocarcinoma (PDAC) represents a major global health problem that causes over 200000 deaths each year worldwide. The disease is highly resistant to cytotoxic and targeted therapies and the average survival is less than 12 months. This situation prompted Alessandro Carugo and Giulio Draetta to develop a novel genetic mouse system, termed Patient-Based In Vivo Lethality to Optimize Treatment (PILOT), to perform functional RNAi-based in vivo screens to uncover and target PDAC drivers. In a forward genetic screen focused on epigenetic modifiers, a WDR5-Myc axis that regulates the DNA replication checkpoint was identified and exploited in vivo for therapeutic intervention...
August 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741488/extraordinary-cancer-epigenomics-thinking-outside-the-classical-coding-and-promoter-box
#14
REVIEW
Matthew Murtha, Manel Esteller
The advent of functional genomics powered by high-throughput sequencing has given us a new appreciation of the genomic sequences that lie outside the canonical promoter-coding sequence box. These regions harbor distant regulatory elements, enhancers, super-enhancers, insulators, alternative promoters, and sequences that transcribe as noncoding RNAs (ncRNAs) such as miRNAs and long ncRNAs. These functional genomics studies have also enabled a clearer understanding of the role of the 3D structure of the genome in epigenetic regulation...
October 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28740569/dna-oncogenic-virus-induced-oxidative-stress-genomic-damage-and-aberrant-epigenetic-alterations
#15
REVIEW
Mankgopo Magdeline Kgatle, Catherine Wendy Spearman, Asgar Ali Kalla, Henry Norman Hairwadzi
Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV). Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28740189/aberrant-methylation-of-meg3-functions-as-a-potential-plasma-based-biomarker-for-cervical-cancer
#16
Jun Zhang, Tingting Yao, Zhongqiu Lin, Yali Gao
Methylation alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. Although MEG3 has been proved to be a tumor suppressor in cervical cancer according to our previous study, the diagnostic value of MEG3 methylation in plasma is still unknown. Therefore, the aim of this study is to identify a novel epigenetic biomarker for cervical cancer. In the current study, the level of MEG3 methylation was evaluated using methylation-specific polymerase chain reaction. The results showed that the level of MEG3 methylation was significantly higher in cervical cancer tissues and patients' plasmas than those in adjacent normal tissues and plasmas of healthy participants respectively...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738804/oncogenic-long-noncoding-rna-landscape-in-breast-cancer
#17
Shouping Xu, Dejia Kong, Qianlin Chen, Yanyan Ping, Da Pang
BACKGROUND: Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified. METHODS: Oncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation...
July 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28737768/arid1a-mutated-ovarian-cancers-depend-on-hdac6%C3%A2-activity
#18
Benjamin G Bitler, Shuai Wu, Pyoung Hwa Park, Yang Hai, Katherine M Aird, Yemin Wang, Yali Zhai, Andrew V Kossenkov, Ana Vara-Ailor, Frank J Rauscher Iii, Weiping Zou, David W Speicher, David G Huntsman, Jose R Conejo-Garcia, Kathleen R Cho, David W Christianson, Rugang Zhang
ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with this genetic characteristic remain to be explored. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours...
July 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28737694/the-role-of-p16-ink4a-pathway-in-human-epidermal-stem-cell-self-renewal-aging-and-cancer
#19
REVIEW
Daniela D'Arcangelo, Lavinia Tinaburri, Elena Dellambra
The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16(INK4a) is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16(INK4a) governs the processes of SC self-renewal in several tissues and its deregulation may result in aging or tumor development...
July 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28736730/new-insight-into-microrna-functions-in-cancer-oncogene-microrna-tumor-suppressor-gene-network
#20
REVIEW
Kecheng Zhou, Minxia Liu, Yi Cao
Tumorigenesis is a multi-step and complex process with multi-factors involved. Deregulated oncogenes and tumor suppressor genes (TSGs) induced by genetic and epigenetic factors are considered as the driving force in the development and progression of cancer. Besides, microRNAs (miRNAs) act vital roles in tumorigenesis through regulating some oncogenes and TSGs. Interestingly, miRNAs are also regulated by oncogenes and TSGs. Considering the entangled regulation, here we propose a new insight into these regulation relationships in cancer: oncogene-miRNA-TSG network, which further emphasizes roles of miRNA, as well as highlights the network regulation among oncogene, miRNA, and TSG during tumorigenesis...
2017: Frontiers in Molecular Biosciences
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