Xiaoxuan Yu, Hui Li, Po Hu, Yingjie Qing, Xiangyuan Wang, Mengyuan Zhu, Hongzheng Wang, Zhanyu Wang, Jingyan Xu, Qinglong Guo, Hui Hui
BACKGROUND: Although targeting histone deacetylases (HDACs) may be an effective strategy for core binding factor-acute myeloid leukemia (CBF-AML) harboring t(8;21) or inv(16), HDAC inhibitors are reported to be limited by drug-resistant characteristic. Our purpose is to evaluate the anti-leukemia effects of Baicalein on CBF-AML and clarify its underlying mechanism. METHODS: Enzyme activity assay was used to measure the activity inhibition of HDACs. Rhodamine123 and RT-qPCR were employed to evaluate the distribution of drugs and the change of ATP-binding cassette (ABC) transporter genes...
August 2020: Clinical and Translational Medicine
Jaewang Lee, Ji Hyeon You, Min-Su Kim, Jong-Lyel Roh
Ferroptosis is a newly defined form of cell death induced by iron-dependent accumulation of lethal lipid peroxidation. Ferroptosis represent a therapeutic strategy to suppress therapy-resistant cancer cells with more property of epithelial-mesenchymal transition (EMT). However, epigenetic reprogramming of EMT has been rarely studied in the context of ferroptosis susceptibility. Therefore, we examined the therapeutic potentiality of EMT epigenetic reprogramming in promoting ferroptosis in head and neck cancer (HNC) cells...
August 28, 2020: Redox Biology
Bowen Li, Jingwen Jiang, Yehuda G Assaraf, Hengyi Xiao, Zhe-Sheng Chen, Canhua Huang
Despite the development of targeted therapy, drug resistance remains a primary hindrance to curative treatment of various cancers. Among several novel approaches to overcome drug resistance, modulating N6 -methyladenosine (m6 A) RNA modification was found to be an important strategy in various types of cancer cells. Considered as one of the most common epigenetic RNA modifications, m6 A regulates multiple biological processes including cellular proliferation, metabolism, and metastasis through modulation of RNA splicing, degradation, and translation, leading to anticancer drug resistance...
August 20, 2020: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Peng Chen, Wen-Fu Xiao, Min-Hui Pan, Jin-Shu Xiao, Yu-Jie Feng, Zhan-Qi Dong, Bang-Xing Zou, Li Zhou, You-Hong Zhang, Cheng Lu
DNA methylation is an important epigenetic modification and has been shown to be involved in the response to abiotic stress. However, there are few studies on DNA methylation in insect response to environmental signals. In this study, we conducted a comprehensive comparative analysis of DNA methylation profiles between two silkworm strains with significantly different resistance to heat and humidity by whole-genome bisulfite sequencing (WGBS). We identified, in total, 2934 differentially methylated regions (DMRs) between RT_48h (resistant strain with high-temperature/humidity treatment for 48 h) and ST_48h (sensitive strain with high-temperature/humidity treatment for 48 h) under cytosine context (CG), which corresponded to 1230 DMR-related genes (DMGs), and the DMRs were primarily located in the gene body (exon and intron) region...
September 3, 2020: International Journal of Biological Macromolecules
Santosh Shenoy
Cell plasticity, also known as lineage plasticity is defined as the ability of a cell to reprogram and change its phenotype identity. Cell plasticity is context dependent and occurs during the development of an embryo, tissue regeneration, wound healing. However when deregulated and aberrant it also contributes to cancer initiation, progression, metastases and resistance to therapies. Tumors cells exhibit varying forms of cell plasticity in each stage of the disease to evade normal regulation as would have occurred in normal cell division and homeostasis...
September 2020: Surgical Oncology
Eric H Kim, Dengfeng Cao, Nupam P Mahajan, Gerald L Andriole, Kiran Mahajan
The androgen receptor (AR) is a critical transcription factor in prostate cancer (PC) pathogenesis. Its activity in malignant cells is dependent on interactions with a diverse set of co-regulators. These interactions fluctuate depending on androgen availability. For example, the androgen depletion increases the dependence of castration-resistant PCs (CRPCs) on the ACK1 and HOXB13 cell survival pathways. Activated ACK1, an oncogenic tyrosine kinase, phosphorylates cytosolic and nuclear proteins, thereby avoiding the inhibitory growth consequences of androgen depletion...
September 2020: NAR cancer
Yasen Maimaitiyiming, Qian Qian Wang, Chih-Hung Hsu, Hua Naranmandura
Epigenetic alterations regulate gene expression without changes in the DNA sequence. It is well-demonstrated that aberrant epigenetic changes contribute to the leukemogenesis of acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) is one of the most common drugs used in the frontline treatment of APL that act through targeting and destabilizing the PML/RARα oncofusion protein. ATO together with all-trans retinoic acid (ATRA) lead to durable remission of more than 90% non-high-risk APL patients, turning APL treatment into a paradigm of oncoprotein targeted cure...
August 31, 2020: Toxicology and Applied Pharmacology
Kevin A Murach, C Brooks Mobley, Christopher J Zdunek, Kaitlyn K Frick, Savannah R Jones, John J McCarthy, Charlotte A Peterson, Cory M Dungan
BACKGROUND: In the context of mass regulation, 'muscle memory' can be defined as long-lasting cellular adaptations to hypertrophic exercise training that persist during detraining-induced atrophy and may facilitate future adaptation. The cellular basis of muscle memory is not clearly defined but may be related to myonuclear number and/or epigenetic changes within muscle fibres. METHODS: Utilizing progressive weighted wheel running (PoWeR), a novel murine exercise training model, we explored myonuclear dynamics and skeletal muscle miRNA levels with training and detraining utilizing immunohistochemistry, single fibre myonuclear analysis, and quantitative analysis of miRNAs...
September 2, 2020: Journal of Cachexia, Sarcopenia and Muscle
Duolan Naren, Tianyou Yan, Yuping Gong, Jingcao Huang, Dan Zhang, Lina Sang, Xue Zheng, Yarong Li
PURPOSE: Acute myeloid leukemia (AML) is a heterogenous disease and the survival of AML patients is largely attributed to the improvement of supportive treatment. Wilms' tumor 1-associated protein (WTAP) is a nuclear protein functions in many physiological and pathological processes. Although its expression and function in many malignant diseases have been reported, its prognostic and epigenetic roles in AML are largely unknown. METHODS: Peripheral blood or bone marrow samples were collected from AML patients...
September 3, 2020: Journal of Cancer Research and Clinical Oncology
Sabah Akhtar, Shireen Hourani, Lubna Therachiyil, Abdullah Al-Dhfyan, Abdelali Agouni, Asad Zeidan, Shahab Uddin, Hesham M Korashy
Compelling evidence has demonstrated that tumor bulk comprises distinctive subset of cells generally referred as cancer stem cells (CSCs) that has been proposed as a strong sustainer and promoter of tumorigenesis and therapeutic resistance. These distinguished properties of CSCs have raised interest in understanding the molecular mechanisms that govern the maintenance of these cells. Numerous experimental and epidemiological studies have demonstrated that exposure to environmental toxins such as the polycyclic aromatic hydrocarbons (PAHs) is strongly involved in cancer initiation and progression...
August 30, 2020: Seminars in Cancer Biology
RobertK Suter, Jezabel Rodriguez-Blanco, Nagi G Ayad
Clinical studies have shown that treating many primary brain tumors is challenging due in part to the lack of safe and effective compounds that cross the blood brain barrier (BBB) (Tan et al., 2018). However, if we were to imagine that we have ideal BBB penetrant compounds that target brain tumor cells selectively, recent studies suggest that those compounds may still not be effective due to the heterogenous nature of the tumors. In other words, there are many subsets of cells within a brain tumor and we need compounds to target all those different populations...
August 30, 2020: Neurobiology of Disease
Emilyn U Alejandro, Seokwon Jo, Brian Akhaphong, Pau Romaguera Llacer, Maya Gianchandani, Brigid Gregg, Sebastian D Parlee, Ormond A MacDougald, Ernesto Bernal-Mizrachi
Maternal low-protein diet (LP) throughout gestation affects pancreatic β-cell fraction of the offspring at birth, thus increasing their susceptibility to type 2 diabetes in adulthood. The present study sought to strictly examine the effects of LP during the last week of gestation (LP12.5) as a developmental window for β-cell programming and metabolic dysfunction in adulthood. Islet morphology analysis revealed normal β-cell fraction in LP12.5 newborns. Normal glucose tolerance was observed in 6-8 weeks old male and female LP12...
September 2, 2020: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Zhengyi Wang, Xiaoying Wu
Immunocheckpoint proteins of tumor infiltrating lymphocytes play an important role in tumor prognosis in the course of tumor clinicopathology. PD-1 (Programmed cell death protein 1) is an important immunosuppressive molecule. By binding to PD-L1 (programmed cell death-ligand 1), it blocks TCR and its costimulus signal transduction, inhibits the activation and proliferation of T cells, depletes the function of effector T cells, and enables tumor cells to achieve immune escape. In recent years, immunocheckpoint blocking therapy targeting the PD-1/PD-L1 axis has achieved good results in a variety of malignant tumors, pushing tumor immunotherapy to a new milestone, such as anti-PD-1 monoclonal antibody Nivolumab, Pembrolizumab, and anti-PD-L1 monoclonal antibody Atezolizumab, which are considered as potential antitumor drugs...
September 2, 2020: Cancer Medicine
Maxime Janin, Manel Esteller
In this issue, Deblois and colleagues show how taxane-resistant triple-negative breast cancer cells evade viral mimicry response as a result of metabolic alteration, DNA hypomethylation, and relocation of histone H3K27 trimethylation (H3K27me3). This adaptation confers a therapeutic vulnerability to the inhibition of the H3K27me3 methyltransferase EZH2 in resistant cells, leading to tumor growth inhibition by viral mimicry reactivation. See related article by Deblois et al., p. 1312 .
September 2020: Cancer Discovery
Andrew D Klocko, Calvin A Summers, Marissa L Glover, Robert Parrish, William K Storck, Kevin J McNaught, Nicole D Moss, Kirsten Gotting, Aurelian Stewart, Ariel M Morrison, Laurel Payne, Shin Hatakeyama, Eric U Selker
DNA methylation, a prototypical epigenetic modification implicated in gene silencing, occurs in many eukaryotes and plays a significant role in the etiology of diseases such as cancer. The filamentous fungus Neurospora crassa places DNA methylation at regions of constitutive heterochromatin such as in centromeres and in other A:T-rich regions of the genome, but this modification is dispensable for normal growth and development. This and other features render N. crassa an excellent model to genetically dissect elements of the DNA methylation pathway...
September 1, 2020: Genetics
Raquel Silva Dos Reis, Jéssica Aflávio Dos Santos, Priscila Marinho de Abreu, Raquel Spinassé Dettogni, Eldamária de Vargas Wolfgramm Dos Santos, Elaine Stur, Lidiane Pignaton Agostini, Quézia Silva Anders, Lyvia Neves Rebello Alves, Isabella Bittencourt do Valle, Marília Arantes Lima, Evandro Duccini Souza, José Roberto Vasconcelos Podestá, Sandra Ventorin von Zeidler, Melissa de Freitas Cordeiro-Silva, Iúri Drumond Louro
Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR...
August 21, 2020: Genetics and Molecular Biology
Fauzia Zarreen, Supriya Chakraborty
Geminiviruses constitute one of the largest families of plant viruses infecting many economically important crops. The proteins encoded by the single-stranded DNA genome of geminiviruses interact with a wide range of host proteins to cause global dysregulation of cellular processes and help establish infection in the host. Geminiviruses have evolved numerous mechanisms to exploit host epigenetic processes to ensure viral genome replication and survival. Here we discuss the current knowledge of diverse epigenetic processes such as DNA methylation, histone post-transcriptional modification, chromatin remodelling and nucleosome repositioning that have been implicated in the regulation of geminivirus pathogenesis...
September 1, 2020: Journal of Experimental Botany
Dong Woo Kang, Won Chan Hwang, Yu Na Noh, Youra Kang, Younghoon Jang, Jung-Ae Kim, Do Sik Min
Glioblastoma (GBM) is an aggressive brain tumor and drug resistance remains a major barrier for therapeutics. Epigenetic alterations are implicated in GBM pathogenesis, and epigenetic modulators including histone deacetylase (HDAC) inhibitors are exploited as promising anticancer therapies. Here, we demonstrate that phospholipase D1 (PLD1) is a transcriptional target of HDAC inhibitors and confers resistance to HDAC inhibitor in GBM. Treatment of vorinostat upregulates PLD1 through PKCζ-Sp1 axis. Vorinostat induces dynamic changes in the chromatin structure and transcriptional machinery associated with PLD1 promoter region...
September 1, 2020: Journal of Cellular Physiology
Udhayakumar Gopal, Salvatore V Pizzo
Cancer cells acquire dysregulated gene expression to establish specific transcriptional dependencies and their underlying mechanisms that are ultimately responsible for this addictions have not been fully elucidated. Glucose-regulated protein 78 (GRP78) is a stress-inducible, multifunctional, prosurvival, endoplasmic reticulum chaperone in the heat shock protein 70 family. Expression of cell surface GRP78 (CS-GRP78) is associated with increased malignant behavior and resistance to chemotherapy and radiotherapy by endowing various cancer cells with increased proliferative ability, altered metabolism, improved survival, and augmented invasive and metastatic potential...
August 31, 2020: Journal of Cellular Physiology
Alessandro Rizzo, Angela Dalia Ricci, Simona Tavolari, Giovanni Brandi
Peripheral blood of cancer patients "physiologically" presents cells and cellular components deriving from primary or metastatic sites, including circulating tumor cells (CTCs), circulating free DNA (cfDNA) and exosomes containing proteins, lipids and nucleic acids. The term circulating tumor DNA (ctDNA) indicates the part of cfDNA which derives from primary tumors and/or metastatic sites, carrying tumor-specific genetic or epigenetic alterations. Analysis of ctDNA has enormous potential applications in all stages of cancer management, including earlier diagnosis of cancer, identification of driver alterations, monitoring of treatment response and detection of resistance mechanisms...
September 2020: Cancer Genomics & Proteomics
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