Epigenetics of Modified DNA Bases: 5-Methylcytosine and Beyond DOI Creative Commons
Suresh Kumar, Viswanathan Chinnusamy,

Trilochan Mohapatra

et al.

Frontiers in Genetics, Journal Year: 2018, Volume and Issue: 9

Published: Dec. 18, 2018

Modification of DNA bases plays vital roles in the epigenetic control gene expression both animals and plants. Though much attention is given to conventional signature 5-methylcytosine (5-mC), field epigenetics attracting increased scientific interest through discovery additional modifications their controlling expression. Theoretically, each can be modified; however, cytosine adenine only are known so far. This review focuses on recent findings well-studied yet poorly characterized modification which serve as an layer regulation discuss potential Cytosine at symmetric (CG, CHG) asymmetric (CHH) contexts a key feature. In addition ROS1 family mediated demethylation, Ten-Eleven Translocation proteins-mediated hydroxylation 5-mC 5-hydroxymethylcytosine active demethylation pathway also discussed. The marks associated with several cellular developmental processes, pluripotency stem cells, neuron cell development, tumor development animals. Therefore, most recently discovered N6-methyladenine, mark regulatory potential, described. Interestingly, these newly found genomes lack canonical 5-mC, signifying independent functions. These modified considered important players epigenomics. for combinatorial interaction among suggests that codon likely substantially more complicated than it thought today.

Language: Английский

Combination therapy in combating cancer DOI Open Access

Reza Bayat Mokhtari,

Tina S. Homayouni,

Narges Baluch

et al.

Oncotarget, Journal Year: 2017, Volume and Issue: 8(23), P. 38022 - 38043

Published: March 30, 2017

// Reza Bayat Mokhtari 1,2,4 , Tina S. Homayouni 1 Narges Baluch 3 Evgeniya Morgatskaya Sushil Kumar Bikul Das 4 and Herman Yeger 1,2 Developmental Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada 2 Department of Paediatric Laboratory Medicine, Children Institute Medical Science, University Pathology Molecular Queen’s University, Kingston, Immunology Infectious Diseases, Forsyth Institute, Cambridge, Massachusetts, USA Correspondence to: Yeger, email: Mokhtari, Keywords : Nrf2-Keap1, HIF-1alpha, carbonic anhydrase 9 (CAIX), histone deacetylase inhibitor (HDACi), (CAI) Received October 19, 2016 Accepted February 27, 2017 Published March 30, Abstract Combination therapy, a treatment modality that combines two or more therapeutic agents, is cornerstone cancer therapy. amalgamation anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in characteristically synergistic an additive manner. This potentially reduces drug resistance, while simultaneously providing benefits, such as reducing tumour growth metastatic potential, arresting mitotically active cells, stem cell populations, inducing apoptosis. 5-year survival rates most cancers are still quite low, process developing new costly extremely time-consuming. Therefore, strategies target provide efficient effective results at affordable cost being considered. One incorporates repurposing agents initially used different diseases other than cancer. primarily when FDA-approved agent similar found Because one combination therapy already FDA-approved, overall costs research reduced. increases efficiency thereby benefiting “medically underserved”. In addition, repurposed pharmaceutical with therapeutics has shown promising mitigating burden. this systematic review, we discuss important commonly targeted Furthermore, also review primary have gained popularity clinical trials since 2012.

Language: Английский

Citations

2023
Epigenetic plasticity and the hallmarks of cancer DOI Open Access
William Flavahan, Elizabeth Gaskell, B Bernstein

et al.

Science, Journal Year: 2017, Volume and Issue: 357(6348)

Published: July 20, 2017

Cancer epigenetics in the driver's seat Recent cancer genome projects unexpectedly highlighted role of epigenetic alterations development. About half human cancers were found to harbor mutations chromatin proteins. In a Review, Flavahan et al. propose that and aberrations have potential confer on cells full range oncogenic properties represented classic “hallmarks” depiction cancer. They suggest genetic, environmental, metabolic factors can make aberrantly permissive or restrictive. Permissive creates state “epigenetic plasticity,” which activate oncogene expression cell fate changes drive Science , this issue p. eaal2380

Language: Английский

Citations

1156
Genetics and biology of prostate cancer DOI Open Access
Guocan Wang, Di Zhao, Denise J. Spring

et al.

Genes & Development, Journal Year: 2018, Volume and Issue: 32(17-18), P. 1105 - 1140

Published: Sept. 1, 2018

Despite the high long-term survival in localized prostate cancer, metastatic cancer remains largely incurable even after intensive multimodal therapy. The lethality of advanced disease is driven by lack therapeutic regimens capable generating durable responses setting extreme tumor heterogeneity on genetic and cell biological levels. Here, we review available model systems, genome atlas, cellular functional microenvironment, tumor-intrinsic tumor-extrinsic mechanisms underlying resistance, technological advances focused detection management. These advances, along with an improved understanding adaptive to conventional therapies, anti-androgen therapy, immunotherapy, are catalyzing development more effective strategies for disease. In particular, knowledge heterotypic interactions between coevolution host cells microenvironment has illuminated novel combinations a strong potential eventual cures Improved management will also benefit from artificial intelligence-based expert decision support systems proper standard care, prognostic determinant biomarkers minimize overtreatment disease, new standards care accelerated next-generation clinical trials.

Language: Английский

Citations

641
Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity DOI Open Access
Shannon Lee, Jens Rauch, Walter Kölch

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 1102 - 1102

Published: Feb. 7, 2020

Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous signal transduction that regulate all aspects of life and are frequently altered in disease. Here, we focus on the role MAPK modulating drug sensitivity resistance cancer. We briefly discuss new findings extracellular signaling-regulated (ERK) pathway, but mainly mechanisms how stress activated pathways, such as p38 Jun N-terminal kinases (JNK), impact response cancer cells to chemotherapies targeted therapies. In this context, also metabolic epigenetic aberrations therapeutic opportunities arising from these changes.

Language: Английский

Citations

637
Principles of DNA methylation and their implications for biology and medicine DOI
Yuval Dor, Howard Cedar

The Lancet, Journal Year: 2018, Volume and Issue: 392(10149), P. 777 - 786

Published: Aug. 9, 2018

Language: Английский

Citations

544
The Key Role of Epigenetics in Human Disease Prevention and Mitigation DOI
Andrew P. Feinberg

New England Journal of Medicine, Journal Year: 2018, Volume and Issue: 378(14), P. 1323 - 1334

Published: April 4, 2018

Epigenetics is the regulation of gene expression through alterations in DNA or associated factors (other than sequence). These control diverse manifestations diseases. Insights into epigenetic modification may lead to new therapies for common

Language: Английский

Citations

519
Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA DOI Creative Commons
Min Wang, Chao Mao,

Lianlian Ouyang

et al.

Cell Death and Differentiation, Journal Year: 2019, Volume and Issue: 26(11), P. 2329 - 2343

Published: Feb. 20, 2019

The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional translational regulation, is involved cancer. However, the circuitry lncRNAs tumorigenesis remains elusive. Here we demonstrate that nuclear lncRNA LINC00336 upregulated lung cancer functions as an oncogene by acting competing endogenous RNA (ceRNAs). bound RNA-binding protein ELAVL1 (ELAV-like 1) using nucleotides 1901–2107 of RRM interaction domain key amino acids (aa) (aa 101–213), inhibiting ferroptosis. Moreover, increased expression stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) through p53 signaling pathway, further supporting hypothesis promotes expression. Interestingly, served sponge microRNA 6852 (MIR6852) to regulate cystathionine-β-synthase (CBS), surrogate marker Finally, found MIR6852 inhibited cell growth promoting These data show network ceRNA important

Language: Английский

Citations

481
The impact of cellular metabolism on chromatin dynamics and epigenetics DOI
Michael A. Reid, Ziwei Dai, Jason W. Locasale

et al.

Nature Cell Biology, Journal Year: 2017, Volume and Issue: 19(11), P. 1298 - 1306

Published: Oct. 23, 2017

Language: Английский

Citations

442
Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis DOI
Oliver G. McDonald, Xin Li,

Tyler Saunders

et al.

Nature Genetics, Journal Year: 2017, Volume and Issue: 49(3), P. 367 - 376

Published: Jan. 16, 2017

Language: Английский

Citations

432
Heterochromatin: Guardian of the Genome DOI Open Access
Aniek Janssen, Serafin U. Colmenares, Gary H. Karpen

et al.

Annual Review of Cell and Developmental Biology, Journal Year: 2018, Volume and Issue: 34(1), P. 265 - 288

Published: July 25, 2018

Constitutive heterochromatin is a major component of the eukaryotic nucleus and essential for maintenance genome stability. Highly concentrated at pericentromeric telomeric domains, riddled with repetitive sequences has evolved specific ways to compartmentalize, silence, repair repeats. The delicate balance between epigenetic cellular processes such as mitosis DNA replication reveals highly dynamic plastic chromatin domain that can be perturbed by multiple mechanisms, far-reaching consequences integrity. Indeed, dysfunction provokes genetic turmoil inducing aberrant repeat repair, chromosome segregation errors, transposon activation, stress strongly implicated in aging tumorigenesis. Here, we summarize general principles structure function, discuss importance its integrity, propose more comprehensive analyses roles tumorigenesis will integral future innovations cancer treatment.

Language: Английский

Citations

427