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Cancer epigenetics

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https://www.readbyqxmd.com/read/29778718/nimbolide-epigenetically-regulates-autophagy-and-apoptosis-in-breast-cancer
#1
Venkatesh Pooladanda, Soumya Bandi, Sandhya Rani Mondi, Krishna Mohan Gottumukkala, Chandraiah Godugu
Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29778644/a-trichostatin-a-tsa-sp1-mediated-mechanism-for-the-regulation-of-sall2-tumor-suppressor-in-jurkat-t-cells
#2
Matías I Hepp, David Escobar, Carlos Farkas, Viviana Hermosilla, Claudia Álvarez, Roberto Amigo, José L Gutiérrez, Ariel F Castro, Roxana Pincheira
SALL2 is a transcription factor involved in development and disease. Deregulation of SALL2 has been associated with cancer, suggesting that it plays a role in the disease. However, how SALL2 is regulated and why is deregulated in cancer remain poorly understood. We previously showed that the p53 tumor suppressor represses SALL2 under acute genotoxic stress. Here, we investigated the effect of Histone Deacetylase Inhibitor (HDACi) Trichostatin A (TSA), and involvement of Sp1 on expression and function of SALL2 in Jurkat T cells...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29778234/egfl7-and-rassf1-promoter-hypermethylation-in-epithelial-ovarian-cancer
#3
Yanisa Rattanapan, Veerawat Korkiatsakul, Adcharee Kongruang, Takol Chareonsirisuthigul, Budsaba Rerkamnuaychoke, Anna Wongkularb, Sarikapan Wilailak
DNA methylation is one of the epigenetic mechanisms associated with gene expression and plays a key role as in activation and deactivation of oncogenes and tumor suppressor genes, respectively. This study employed DNA methylation array to identify methylated genes which are highly correlated with various phenotypes of epithelial ovarian cancer (EOC) in Thai patients and to quantify promoter CpG-island methylation of candidate genes. Tissues from patients with serous and non-serous EOC showed significantly higher promoter methylation of EGFL7 and RASSF1 compared to benign cases...
August 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29777275/overexpression-of-abcb4-contributes-to-acquired-doxorubicin-resistance-in-breast-cancer-cells-in-vitro
#4
Jia-Feng Huang, Chun-Jie Wen, Guo-Zhi Zhao, Yi Dai, Ying Li, Lan-Xiang Wu, Hong-Hao Zhou
PURPOSE: Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism. METHODS: In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry...
May 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29775961/antioxidant-response-elements-discovery-classes-regulation-and-potential-applications
#5
REVIEW
Azhwar Raghunath, Kiruthika Sundarraj, Raju Nagarajan, Frank Arfuso, Jinsong Bian, Alan P Kumar, Gautam Sethi, Ekambaram Perumal
Exposure to antioxidants and xenobiotics triggers the expression of a myriad of genes encoding antioxidant proteins, detoxifying enzymes, and xenobiotic transporters to offer protection against oxidative stress. This articulated universal mechanism is regulated through the cis-acting elements in an array of Nrf2 target genes called antioxidant response elements (AREs), which play a critical role in redox homeostasis. Though the Keap1/Nrf2/ARE system involves many players, AREs hold the key in transcriptional regulation of cytoprotective genes...
May 7, 2018: Redox Biology
https://www.readbyqxmd.com/read/29775753/long-non-coding-rna-biomarker-for-human-laryngeal-squamous-cell-carcinoma-prognosis
#6
Jingjing Chen, Zhisen Shen, Hongxia Deng, Wei Zhou, Qi Liao, Ying Mu
Long non-coding RNAs (lncRNA) were discovered in tumors. The regulation of lncRNA in human laryngeal squamous cell carcinoma (LSCC) remains incomplete. Uncovering the potential of lncRNA to stratify the prognosis of LSCC and streamline the vast amount of clinical information will affect medical interventions. The surgical resected LSCC tissues, adjacent non-cancerous tissues (ANCT) and lymph node metastatic tissue (LNM) were collected from 76 patients for lncRNA AC008440.10 expression assay. The stages of LSCC and LNM were classified accordingly...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775654/targeting-cancer-s-metabolic-co-dependencies-a-landscape-shaped-by-genotype-and-tissue-context
#7
REVIEW
Junfeng Bi, Sihan Wu, Wenjing Zhang, Paul S Mischel
Tumors cells reprogram their metabolism to fuel rapid growth. The ability to trace nutrient fluxes in the context of specific alterations has provided new mechanistic insight into the process of oncogenic transformation. A broad array of complementary genetic, epigenetic, transcriptional and translational mechanisms has been identified, revealing a metabolic landscape of cancer. However, cancer metabolism is not a static or uniform process, including within a single tumor. Tumor cells adapt to changing environmental conditions, profoundly shaping the enzymatic dependencies of individual cells...
May 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29774218/new-insights-of-helicobacter-pylori-host-pathogen-interactions-the-triangle-of-virulence-factors-epigenetic-modifications-and-non-coding-rnas
#8
REVIEW
Farzam Vaziri, Samira Tarashi, Abolfazl Fateh, Seyed Davar Siadat
Helicobacter pylori ( H. pylori ) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important...
May 16, 2018: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/29774131/methylation-of-dna-and-chromatin-as-a-mechanism-of-oncogenesis-and-therapeutic-target-in-neuroblastoma
#9
REVIEW
Ram Mohan Ram Kumar, Nina Felice Schor
Neuroblastoma (NB), a developmental cancer, is often fatal, emphasizing the need to understand its pathogenesis and identify new therapeutic targets. The heterogeneous pathological and clinical phenotype of NB underscores the cryptic biological and genetic features of this tumor that result in outcomes ranging from rapid progression to spontaneous regression. Despite recent genome-wide mutation analyses, most primary NBs do not harbor driver mutations, implicating epigenetically-mediated gene regulatory mechanisms in the initiation and maintenance of NB...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#10
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#11
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774081/g9a-stimulates-crc-growth-by-inducing-p53-lys373-dimethylation-dependent-activation-of-plk1
#12
Jie Zhang, Yafang Wang, Yanyan Shen, Pengxing He, Jian Ding, Yi Chen
Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a...
2018: Theranostics
https://www.readbyqxmd.com/read/29773832/distinct-epigenetic-landscapes-underlie-the-pathobiology-of-pancreatic-cancer-subtypes
#13
Gwen Lomberk, Yuna Blum, Rémy Nicolle, Asha Nair, Krutika Satish Gaonkar, Laetitia Marisa, Angela Mathison, Zhifu Sun, Huihuang Yan, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Tamas Ordog, Jeong-Heon Lee, Gavin Oliver, Eric Klee, Vincent Moutardier, Odile Gayet, Benjamin Bian, Pauline Duconseil, Marine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien De Reyniès, Nelson Dusetti, Juan Iovanna, Raul Urrutia
Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773061/development-of-novel-therapeutics-targeting-isocitrate-dehydrogenase-mutations-in-cancer
#14
Horrick Sharma
Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH 1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumor types, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyze αKG conversion to (R)-2-hydroxyglutarate ((R)-2HG)...
May 17, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#15
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772566/the-epigenetic-factor-kdm2b-regulates-emt-and-small-gtpases-in-colon-tumor-cells
#16
Nefeli Zacharopoulou, Anna Tsapara, Galatea Kallergi, Evi Schmid, Saad Alkahtani, Saud Alarifi, Philip N Tsichlis, Sotirios C Kampranis, Christos Stournaras
BACKGROUND/AIMS: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. METHODS: We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins...
May 14, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29772561/thyroid-cancer-phenotypes-in-relation-to-inflammation-and-autoimmunity
#17
Loredana Pagano, Chiara Mele, Maria Teresa Sama, Marco Zavattaro, Marina Caputo, Lucrezia De Marchi, Samuele Paggi, Flavia Prodam, Gianluca Aimaretti, Paolo Marzullo
Thyroid cancer represents the most frequent endocrine neoplasm and is epidemiologically linked to a growing incidence worldwide, which is only in part explained by the increased detection of small cancers in a preclinical stage. Understanding the molecular pathogenesis of well-differentiated thyroid cancers and poorly-differentiated thyroid cancers has prompted interest into the identification of crucial signaling pathways and molecular derangements related to genetic and epigenetic alterations. Increasing attention has been recently focused on inflammation and immunity as major culprit mechanisms involved in thyroid tumourigenesis, through the detection of activated immune cells, pro-inflammatory cytokines, as well as signal integrations between inflammatory and proliferative pathways within the thyroid tumour micro-environment...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772549/long-non-coding-rna-and-polycomb-an-intricate-partnership-in-cancer-biology
#18
Cyrinne Achour, Francesca Aguilo
High-throughput analyses have revealed that the vast majority of the transcriptome does not code for proteins. These non-translated transcripts, when larger than 200 nucleotides, are termed long non-coding RNAs (lncRNAs), and play fundamental roles in diverse cellular processes. LncRNAs are subject to dynamic chemical modification, adding another layer of complexity to our understanding of the potential roles that lncRNAs play in health and disease. Many lncRNAs regulate transcriptional programs by influencing the epigenetic state through direct interactions with chromatin-modifying proteins...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772433/lncrna-sox21-as1-is-associated-with-progression-of-hepatocellular-carcinoma-and-predicts-prognosis-through-epigenetically-silencing-p21
#19
Congxin Wei, Hong Wang, Fei Xu, Zeng Liu, Runde Jiang
Long non-coding RNAs (lncRNAs) have been widely reported in various cancers due to their special molecular mechanisms. LncRNA SOX21-AS1 has been discovered to be a tumor facilitator in several types of human cancers. However, the expression pattern, clinical value and biological effects in hepatocellular carcinoma (HCC) are still unknown. In this study, we detected the high expression level of SOX21-AS1 in tumor tissues and cell lines through performing qRT-PCR analysis. The prognostic value of SOX21-AS1 was identified...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29772428/lncrna-h19-interacts-with-s-adenosylhomocysteine-hydrolase-to-regulate-line-1-methylation-in-human-lung-derived-cells-exposed-to-benzo-a-pyrene
#20
Ye Fu, Wubin Wang, Xuejing Li, Yanli Liu, Yingying Niu, Bin Zhang, Jisheng Nie, Baolong Pan, Ruisheng Wang, Jin Yang
Benzo [a]pyrene (BaP) have been demonstrated to induce lung cancer risk in humans and many different animal models, with aberrant gene methylation as one of the epigenetic errors; however, the molecular mechanisms remain unclear. Here, we used three types of human lung-derived cells with BaP exposure as a model and attempted to investigate the long non-coding RNA (lncRNA) H19/S-adenosylhomocysteine hydrolase (SAHH) pathway that regulates gene methylation in vitro exposure to BaP. Results showed that compared to the controls, BaP-treated cells H19 expressions were increased in a dose- and time-dependent manner, whereas SAHH protein expressions were decreased...
May 9, 2018: Chemosphere
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