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Epigenetics and cancer

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https://www.readbyqxmd.com/read/29028415/crispr-cas9-mediated-noncoding-rna-editing-in-human-cancers
#1
Jie Yang, Xiaodan Meng, Jinchang Pan, Nan Jiang, Chengwei Zhou, Zhenhua Wu, Zhaohui Gong
Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system...
October 13, 2017: RNA Biology
https://www.readbyqxmd.com/read/29028222/role-of-rbp2-induced-er-and-igf1r-erbb-signaling-in-tamoxifen-resistance-in-breast-cancer
#2
Hee-Joo Choi, Hyeong-Seok Joo, Hee-Young Won, Kyueng-Whan Min, Hyung-Yong Kim, Taekwon Son, Young-Ha Oh, Jeong-Yeon Lee, Gu Kong
Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764)...
April 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29027980/the-plasticizer-bisphenol-a-perturbs-the-hepatic-epigenome-a-systems-level-analysis-of-the-mirnome
#3
Ludivine Renaud, Willian A da Silveira, E Starr Hazard, Jonathan Simpson, Silvia Falcinelli, Dongjun Chung, Oliana Carnevali, Gary Hardiman
Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops a disease that resembles human cancer. Using zebrafish as a systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development...
October 13, 2017: Genes
https://www.readbyqxmd.com/read/29027617/zebrafish-as-a-model-to-study-neuroblastoma-development
#4
REVIEW
Mattie J Casey, Rodney A Stewart
Neuroblastoma is a pediatric solid tumor arising from embryonic neural crest progenitor cells that normally generate the peripheral sympathetic nervous system. As such, the location of neuroblastoma tumors is correlated with the distribution of major post-ganglionic clusters throughout the sympathetic chain, with the highest incidence in the adrenal medulla or lumbar sympathetic ganglia (~65%). Neuroblastoma is an enigmatic tumor that can spontaneously regress with minimal treatment or become highly metastatic and develop resistance to aggressive treatments, including radiation and high-dose chemotherapy...
October 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29027401/identification-of-dna-methylation-associated-gene-signatures-in-endometrial-cancer-via-integrated-analysis-of-dna-methylation-and-gene-expression-systematically
#5
Chuandi Men, Hongjuan Chai, Xumin Song, Yue Li, Huawen Du, Qing Ren
OBJECTIVE: Endometrial cancer (EC) is a common gynecologic cancer worldwide. However, the pathogenesis of EC has not been epigenetically elucidated. Here, this study aims to describe the DNA methylation profile and identify favorable gene signatures highly associated with aberrant DNA methylation changes in EC. METHODS: The data regarding DNA methylation and gene expression were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially methylated CpG sites (DMCs), differentially methylated regions (DMRs), and differentially expressed genes (DEGs) were identified, and the relationship between the 2 omics was further analyzed...
November 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29026785/evaluation-of-p16-ink4%C3%AE-hypermethylation-from-liquid-based-pap-test-samples-in-vietnamese-population
#6
Phuong Kim Truong, Thuan Duc Lao, Thuy Ai Huyen LE
BACKGROUND: Human papillomavirus (HPV) infection has been considered as main cause of cervical cancer. Recently, aberrant DNA methylation at tumor suppressor genes (TSGs), leading to inactivation, has also been an early epigenetic event and cofactor in cervical carcinogenesis. This study was performed to evaluate an association between the hypermethylation of p16(INK4α) gene's promoter and HPV exposure in non-invasive samples (liquid-based papanicolaous samples) in Vietnamese population...
September 2017: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/29025584/regulatory-mechanisms-of-long-noncoding-rnas-on-gene-expression-in-cancers
#7
REVIEW
Weiliang Sun, Yunben Yang, Chunjing Xu, Junming Guo
Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that are non-protein coding transcripts longer than 200 nucleotides. In this review, we introduce the mechanisms by which lncRNAs regulate gene expression in four parts, epigenetic regulation (genetic imprinting and chromatin remodeling), transcriptional regulation (molecular decoy), post-transcriptional regulation (splicing and mRNA decay), and translational regulation. H19, Xist, and others are involved in genomic imprinting. HOTAIR and ANRIL function in chromatin remodeling...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29024573/targeting-mta1-hif-1%C3%AE-signaling-by-pterostilbene-in-combination-with-histone-deacetylase-inhibitor-attenuates-prostate-cancer-progression
#8
Nasir A Butt, Avinash Kumar, Swati Dhar, Agnes M Rimando, Israh Akhtar, John C Hancock, Janice M Lage, Charles R Pound, Jack R Lewin, Christian R Gomez, Anait S Levenson
The metastasis-associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression-related epigenetic regulator, which is overexpressed in hormone-refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate-specific Pten-null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo...
October 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29023917/prmt1-and-jmjd6-dependent-arginine-methylation-regulate-hnf4%C3%AE-expression-and-hepatocyte-proliferation
#9
Jie Zhao, Abby Adams, Ben Roberts, Maura O'Neil, Anusha Vittal, Timothy Schmitt, Sean Kumer, Josiah Cox, Zhuan Li, Steven A Weinman, Irina Tikhanovich
Alcohol is a well-established risk factor for hepatocellular carcinoma, but the mechanisms by which it promotes liver cancer are not well understood. Several studies have shown that cellular protein arginine methylation is inhibited by alcohol. Arginine methylation is controlled by the reciprocal activity of protein arginine methyltransferases, primarily PRMT1, and a demethylase JMJD6. The aim of this study was to explore the role of arginine methylation changes in alcohol pathogenesis. We found that PRMT1 activity is inhibited in livers of mice fed with alcohol compared to pair-fed mice...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29023490/network-modeling-of-kinase-inhibitor-polypharmacology-reveals-pathways-targeted-in-chemical-screens
#10
Oana Ursu, Sara J C Gosline, Neil Beeharry, Lauren Fink, Vikram Bhattacharjee, Shao-Shan Carol Huang, Yan Zhou, Tim Yen, Ernest Fraenkel
Small molecule screens are widely used to prioritize pharmaceutical development. However, determining the pathways targeted by these molecules is challenging, since the compounds are often promiscuous. We present a network strategy that takes into account the polypharmacology of small molecules in order to generate hypotheses for their broader mode of action. We report a screen for kinase inhibitors that increase the efficacy of gemcitabine, the first-line chemotherapy for pancreatic cancer. Eight kinase inhibitors emerge that are known to affect 201 kinases, of which only three kinases have been previously identified as modifiers of gemcitabine toxicity...
2017: PloS One
https://www.readbyqxmd.com/read/29022903/alternative-mechanisms-of-mir-34a-regulation-in-cancer
#11
REVIEW
Eva Slabáková, Zoran Culig, Ján Remšík, Karel Souček
MicroRNA miR-34a is recognized as a master regulator of tumor suppression. The strategy of miR-34a replacement has been investigated in clinical trials as the first attempt of miRNA application in cancer treatment. However, emerging outcomes promote the re-evaluation of existing knowledge and urge the need for better understanding the complex biological role of miR-34a. The targets of miR-34a encompass numerous regulators of cancer cell proliferation, survival and resistance to therapy. MiR-34a expression is transcriptionally controlled by p53, a crucial tumor suppressor pathway, often disrupted in cancer...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29020612/covering-the-stem-cell-explosion-at-the-2017-isscr-conference-in-boston
#12
Thomas Graf
The meeting covered a plethora of rapidly evolving approaches and areas, such as organoid cultures modeling tissues and organs; stem cell-specific metabolites revealing new signaling pathways; single-cell technologies discovering new cell types and exploring stem cell niche interactions; novel methods studying stem cells in aging and cancer; lineage-tracing experiments exploring cell plasticity of tissues before and after injury; epigenetic studies illuminating cell reprogramming; new protocols improving cells for regenerative purposes; and several other timely and exciting topics...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29018892/novel-treatment-opportunities-for-sulfur-mustard-related-cancers-genetic-and-epigenetic-perspectives
#13
REVIEW
Soheila Rahmani, Mohammad Abdollahi
Sulfur mustard (SM), also known as mustard gas, is a chemical weapon which by now has been used in many wars. The most concerning SM toxic effect is probable carcinogenicity. In this study, the genetic and epigenetic mechanisms of SM carcinogenicity, by focusing on treatment of SM-associated malignancies, particularly gene therapeutics, cancer vaccines, and epigenetic medications, have been criticized. The required data were collected through an organized search on valid scientific databases. For SM carcinogenicity due to acute or chronic exposure, the entire original and review articles were evaluated...
October 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29018149/hypothesis-stimulation-of-trained-immunity-as-adjunctive-immunotherapy-in-cancer
#14
REVIEW
Mihai G Netea, Leo A B Joosten, Jos W M van der Meer
Cancer immunotherapy has steadily progressed during the past decades, with checkpoint inhibitor therapy becoming the latest and one of the most promising treatments. Despite the progress, most of the patients do not respond or develop resistance, and novel additional approaches are needed to improve the clinical effectiveness of immunotherapy. Trained immunity (TI) has been described recently as a process of epigenetic and metabolic reprogramming that induces a long-term enhanced function of innate immune cells...
October 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29017567/impairment-of-igf2-gene-expression-in-prostate-cancer-is-triggered-by-epigenetic-dysregulation-of-igf2-dmr0-and-its-interaction-with-klf4
#15
Undraga Schagdarsurengin, Angela Lammert, Natalie Schunk, Diana Sheridan, Stefan Gattenloehner, Klaus Steger, Florian Wagenlehner, Temuujin Dansranjavin
BACKGROUND: Human cancer cells often exhibit impaired IGF2 expression and the underlying mechanisms are multifaceted and complex. Besides the well-known imprinting control region IGF2/H19-ICR, the involvement of a differentially methylated region in the promoter P0 of IGF2 gene (IGF2-DMR0) has been suggested. Here, we evaluate several mechanisms potentially leading to up- and/or down-regulation of IGF2 expression in prostate cancer and present a novel role of Kruppel-like factor 4 (KLF4) as a transcriptional regulator of IGF2 binding in IGF2-DMR0...
October 10, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29016348/parp-1-and-parp-2-activity-in-cancer-induced-cachexia-potential-therapeutic-implications
#16
Esther Barreiro, Joaquim Gea
Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28994387/-the-identity-of-normal-and-cancer-stem-cells
#17
Lucie Laplane, Éric Solary
What is a stem cell? Is stemness an intrinsic or extrinsic property? What role does the microenvironment play in the stemness identity? We distinguish four identities for normal and cancerous stem cells and explore their consequences for therapeutic strategy choice in the oncology setting. Acquisition of genetic and epigenetic alterations during cell transformation and disease progression questions the stability of the stemness property's identity in cancers.
October 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28993790/network-diffusion-based-prioritization-of-autism-risk-genes-identifies-significantly-connected-gene-modules
#18
Ettore Mosca, Matteo Bersanelli, Matteo Gnocchi, Marco Moscatelli, Gastone Castellani, Luciano Milanesi, Alessandra Mezzelani
Autism spectrum disorder (ASD) is marked by a strong genetic heterogeneity, which is underlined by the low overlap between ASD risk gene lists proposed in different studies. In this context, molecular networks can be used to analyze the results of several genome-wide studies in order to underline those network regions harboring genetic variations associated with ASD, the so-called "disease modules." In this work, we used a recent network diffusion-based approach to jointly analyze multiple ASD risk gene lists...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28992434/targeting-epigenetics-in-cancer
#19
Richard L Bennett, Jonathan D Licht
Alterations of genes regulating epigenetic processes are frequently found as cancer drivers and may cause widespread alterations of DNA methylation, histone modification patterns, or chromatin structure that disrupt normal patterns of gene expression. Because of the inherent reversibility of epigenetic changes, inhibitors targeting these processes are promising anticancer strategies. Small molecules targeting epigenetic regulators have been developed recently, and clinical trials of these agents are under way for hematologic malignancies and solid tumors...
October 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28991363/microrna-495-3p-functions-as-a-tumour-suppressor-by-regulating-multiple-epigenetic-modifiers-in-gastric-carcinogenesis
#20
Jung Woo Eun, Hyung Seok Kim, Qingyu Shen, Hee Doo Yang, Sang Yean Kim, Jung Hwan Yoon, Won Sang Park, Jung Young Lee, Suk Woo Nam
MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Here we demonstrate that microRNA-495-3p (miR-495-3p) functions as a potent tumour suppressor by governing ten oncogenic epigenetic modifiers (EMs) in gastric carcinogenesis. From the large cohort transcriptome datasets of gastric cancer (GC) patients available from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we were able to recapitulate fifteen EMs as significantly overexpressed in GC among the 51 EMs that were previously reported to be involved in cancer progression...
October 9, 2017: Journal of Pathology
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