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epigenetic regulation

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https://www.readbyqxmd.com/read/28728079/probucol-ameliorates-renal-injury-in-diabetic-nephropathy-by-inhibiting-the-expression-of-the-redox-enzyme-p66shc
#1
Shikun Yang, Li Zhao, Yachun Han, Yu Liu, Chao Chen, Ming Zhan, Xiaofen Xiong, Xuejing Zhu, Li Xiao, Chun Hu, Fuyou Liu, Zhiguang Zhou, Yashpal S Kanwar, Lin Sun
AIMS: Probucol is an anti-hyperlipidemic agent and a potent antioxidant drug that can delay progression of diabetic nephropathy (DN) and reverses renal oxidative stress in diabetic animal models; however, the mechanisms underlying these effects remain unclear. p66Shc is a newly recognized mediator of mitochondrial ROS production in renal cells under high-glucose (HG) ambience. We previously showed that p66Shc can serve as a biomarker for renal oxidative injury in DN patients and that p66Shc up-regulation is correlated with renal damage in vivo and in vitro...
July 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28725280/single-molecule-quantification-of-5-hydroxymethylcytosine-for-diagnosis-of-blood-and-colon-cancers
#2
Noa Gilat, Tzlil Tabachnik, Amit Shwartz, Tamar Shahal, Dmitry Torchinsky, Yael Michaeli, Gil Nifker, Shahar Zirkin, Yuval Ebenstein
BACKGROUND: The DNA modification 5-hydroxymethylcytosine (5hmC) is now referred to as the sixth base of DNA with evidence of tissue-specific patterns and correlation with gene regulation and expression. This epigenetic mark was recently reported as a potential biomarker for multiple types of cancer, but its application in the clinic is limited by the utility of recent 5hmC quantification assays. We use a recently developed, ultra-sensitive, fluorescence-based single-molecule method for global quantification of 5hmC in genomic DNA...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#3
Austin Gay, Dwight A Towler
PURPOSE OF REVIEW: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis. RECENT FINDINGS: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease...
July 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28723670/quaking-5-suppresses-aggressiveness-of-lung-cancer-cells-through-inhibiting-%C3%AE-catenin-signaling-pathway
#4
Xuexia Zhou, Xuebing Li, Cuiyun Sun, Cuijuan Shi, Dan Hua, Lin Yu, Yanjun Wen, Feng Hua, Qian Wang, Qinghua Zhou, Shizhu Yu
Quaking-5 (QKI-5) belongs to the STAR (signal transduction and activation of RNA) family of RNA binding proteins and functions as a tumor suppressor in several human malignancies. In this study, we attempt to elucidate the role of QKI-5 in the pro-metastasis processes of lung cancer (LC) cells and the underlying mechanisms. We confirmed that QKI-5 was decreased in human LC tissues and cell lines, especially in high-metastatic cells. Moreover, QKI expression was positively correlated with LC patients' survival...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723648/cytosine-5-hydroxymethylation-regulates-vhl-gene-expression-in-renal-clear-cell-carcinoma
#5
En-Guang Ma, Yu-Feng Bai, Wei Cao, Yan Cao, Yong-Gang Huang, Huan-Chen Cheng, Rui-Hua An
Cytosine5-hyxymethylation (5hmC)which is a new epigenetic modification form plays important roles in the development and progression of tumors. In the present study, we observed that levels of 5hmC in the promoter region of Von Hippel-Lindau (VHL) were lower in 97 samples of renal clear cell carcinoma tissue than in matched adjacent benign tissues. Moreover, when the cancer tissue samples were divided based on pathological staging, VHL expression and the level of 5hmC in the VHL promoter were both lower in pathological grade III tumors than in grades I or II...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723643/methyltransferase-g9a-promotes-cervical-cancer-angiogenesis-and-decreases-patient-survival
#6
Ruey-Jien Chen, Chia-Tung Shun, Men-Luh Yen, Chia-Hung Chou, Ming-Chieh Lin
Research suggests that the epigenetic regulator G9a, a H3K9 histone methyltransferase, is involved in cancer invasion and metastasis. Here we show that G9a is linked to cancer angiogenesis and poor patient survival. Invasive cervical cancer has a higher G9a expression than cancer precursors or normal epithelium. Pharmacological inhibition and genetic silencing of G9a suppresses H3K9 methylation, cancer cell proliferation, angiogenesis, and cancer cell invasion/migration, but not apoptosis. Microarray and quantitative reverse transcription polymerase chain reaction analyses reveal that G9a induces a cohort of angiogenic factors that include angiogenin, interleukin-8, and C-X-C motif chemokine ligand 16...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723630/functional-role-of-setd2-bap1-parp-3-and-pbrm1-candidate-genes-on-the-regulation-of-htert-gene-expression
#7
Hannah Linne, Hemad Yasaei, Alison Marriott, Amanda Harvey, Kefah Mokbel, Robert Newbold, Terry Roberts
Narrowing the search for the critical hTERT repressor sequence(s) has identified three regions on chromosome 3p (3p12-p21.1, 3p21.2 and 3p21.3-p22). However, the precise location and identity of the sequence(s) responsible for hTERT transcriptional repression remains elusive. In order to identify critical hTERT repressor sequences located within human chromosome 3p12-p22, we investigated hTERT transcriptional activity within 21NT microcell hybrid clones containing chromosome 3 fragments. Mapping of chromosome 3 structure in a single hTERT-repressed 21NT-#3fragment hybrid clone, revealed a 490kb region of deletion localised to 3p21...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723619/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#8
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723559/kmt2a-and-kmt2b-mediate-memory-function-by-affecting-distinct-genomic-regions
#9
Cemil Kerimoglu, M Sadman Sakib, Gaurav Jain, Eva Benito, Susanne Burkhardt, Vincenzo Capece, Lalit Kaurani, Rashi Halder, Roberto Carlos Agís-Balboa, Roman Stilling, Hendrik Urbanke, Andrea Kranz, A Francis Stewart, Andre Fischer
Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation. We compare the decrease in H3K4 methylation and de-regulation of gene expression in hippocampal neurons of mice with knockdown of either Kmt2a or Kmt2b. Kmt2a and Kmt2b control largely distinct genomic regions and different molecular pathways linked to neuronal plasticity. Finally, we show that the decrease in H3K4 methylation resulting from Kmt2a knockdown partially recapitulates the pattern previously reported in CK-p25 mice, a model for neurodegeneration and memory impairment...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28721828/mir-149-as-a-potential-molecular-target-for-cancer
#10
Suet Hui Ow, Pei Jou Chua, Boon Huat Bay
MicroRNAs (miRNAs) are small, non-coding nucleotides that regulate the expression of proteins. They play major roles in fundamental cellular processes. Aberrant expression of miRNAs has been frequently detected in cancers. miR-149 has been implicated in tumor progression by regulating cellular proliferation, migration, invasion, epithelial-mesenchymal-transition and chemoresistance. There have been reports that miR-149 can function both as an oncogene or tumor suppressor, depending on the type of cancer, thereby giving rise to the possibility of utilizing miR-149 mimics and inhibitors for cancer therapy...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28721820/epigenetic-regulations-in-the-pathogenesis-of-periodontitis
#11
Yu Luo, Xian Peng, Dingyu Duan, Chengcheng Liu, Xin Xu, Xuedong Zhou
Periodontitis is a multifactorial infectious disease that affects a large population worldwide. It involves progressive alveolar bone loss, and if left untreated, can lead to the loosening and subsequent loss of teeth. Oral microorganisms and susceptible host have been proposed to be the prerequisite for the development of periodontitis. Aberrant host immune response is the key factor that leads to the destruction of periodontal tissues. Recently, the involvement of epigenetic modifications in the development of periodontitis has attracted increasing attentions...
July 18, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28720801/mapping-and-characterization-of-g-quadruplexes-in-mycobacterium-tuberculosis-gene-promoter-regions
#12
Rosalba Perrone, Enrico Lavezzo, Erika Riello, Riccardo Manganelli, Giorgio Palù, Stefano Toppo, Roberta Provvedi, Sara N Richter
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720666/inactivation-of-receptor-tyrosine-kinases-reverts-aberrant-dna-methylation-in-acute-myeloid-leukemia
#13
Na Shen, Fei Yan, Jiuxia Pang, Na Zhao, Naseema Gangat, Lai-Chu Wu, Ann M Bode, Aref Al-Kali, Mark R Litzow, Shujun Liu
Purpose: Receptor tyrosine kinases (RTKs) are frequently deregulated in leukemia, yet the biological consequences of this deregulation remain elusive. The mechanisms underlying aberrant methylation, a hallmark of leukemia, are not fully understood. Here we investigated the role of RTKs in methylation abnormalities and characterized the hypomethylating activities of RTK inhibitors.<br />Experimental Design: Whether and how RTKs regulate expression of DNA methyltransferases (DNMTs), tumor suppressor genes (TSGs) as well as global and gene specific DNA methylation were examined...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720596/elongator-regulates-hypocotyl-growth-in-darkness-and-during-photomorphogenesis
#14
Magdalena Woloszynska, Olimpia Gagliardi, Filip Vandenbussche, Steven De Groeve, Luis Alonso Baez, Pia Neyt, Sabine Le Gall, Jorge Fung, Paloma Mas, Dominique Van Der Straeten, Mieke Van Lijsebettens
Elongator promotes RNA polymerase II-mediated transcript elongation through epigenetic activities such as histone acetylation. Elongator regulates growth, development, immune response, sensitivity to drought and abscisic acid. We demonstrate that elo mutants exhibit defective hypocotyl elongation but have a normal apical hook in darkness and are hyposensitive to light during photomorphogenesis. These elo phenotypes are supported by transcriptome changes, i.e. downregulation of circadian clock components, positive regulators of skoto- or photomorphogenesis, hormonal pathways and cell wall biogenesis-related factors...
July 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28720390/epigenetic-regulation-of-epithelial-to-mesenchymal-transition-by-the-lysine-specific-demethylase-lsd1-kdm1a
#15
REVIEW
Susanna Ambrosio, Carmen D Saccà, Barbara Majello
The Lysine-specific demethylase 1, KDM1A/LSD1, plays a central role in the regulation of Pol II transcription through the removal of the activation mark (mono- and dimethyl lysine 4 of histone H3). LSD1 is often deregulated in human cancers, and it is frequently overexpressed in human solid cancers and leukemia. LSD1 regulates the epithelial mesenchymal transition (EMT) in epithelial cells, i.e., the ability to transition into mesenchymal cells, to lose homotypic adhesion and to acquire migratory capacity. From its initial discovery as a component of the Snail complex, multiple studies highlighted the causative role of LSD1 in cell invasiveness and EMT, describing its direct involvement in different molecular processes through the interaction with specific partners...
July 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28720288/potential-adverse-effects-of-engineered-nanomaterials-commonly-used-in-food-on-the-mirnome
#16
Jia Pei Lim, Gyeong Hun Baeg, Dinesh Kumar Srinivasan, S Thameem Dheen, Boon Huat Bay
The emergence of nanotechnology has greatly impacted our daily lives. Multiple products, including cosmetics, pharmaceuticals, electronics and food, are produced with incorporation of nanomaterials (NMs). Nanotechnology has yielded many promising benefits, yet, there remains much uncertainty about the hazards of NMs to humans. Hence, it is important to ensure safety of the users. Although many in vitro and in vivo studies have been carried out on the potential toxicity generated by NMs in food, its effects on the microRNA genome (miRNome) involved in the regulation of gene expression have been poorly understood...
July 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28718380/the-burden-of-genetic-and-epigenetic-traits-in-prematurity
#17
Bruna Ribeiro de Andrade Ramos, Márcia Guimarães da Silva
Despite decades of investigations and accumulated scientific knowledge, preterm birth (PTB) remains a significant burden worldwide. Several mechanisms have been proposed to explain this condition, and a number of risk factors from infectious to behavioral and genetic/epigenetic factors influence this outcome. The heritability of PTB is estimated to be 17% to 36%, which demonstrates that genetic predisposition plays a key role in PTB. Structural DNA modifications without changes in the DNA sequence and post-transcriptional regulation also have an impact on gene expression and thus influence pregnancy outcomes...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28717386/understanding-low-radiation-background-biology-through-controlled-evolution-experiments
#18
Nathanael Lampe, Vincent Breton, David Sarramia, Télesphore Sime-Ngando, David G Biron
Biological experiments conducted in underground laboratories over the last decade have shown that life can respond to relatively small changes in the radiation background in unconventional ways. Rapid changes in cell growth, indicative of hormetic behaviour and long-term inheritable changes in antioxidant regulation have been observed in response to changes in the radiation background that should be almost undetectable to cells. Here, we summarize the recent body of underground experiments conducted to date, and outline potential mechanisms (such as cell signalling, DNA repair and antioxidant regulation) that could mediate the response of cells to low radiation backgrounds...
August 2017: Evolutionary Applications
https://www.readbyqxmd.com/read/28717181/discovery-of-novel-human-gene-regulatory-modules-from-gene-co-expression-and-promoter-motif-analysis
#19
Shisong Ma, Michael Snyder, Savithramma P Dinesh-Kumar
Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif's enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716711/epigenetic-silencing-of-mirna-143-regulates-apoptosis-by-targeting-bcl2-in-human-intervertebral-disc-degeneration
#20
Kangcheng Zhao, Yukun Zhang, Kang Liang, Yu Song, Kun Wang, Shuai Li, Xinghuo Wu, Wenbin Hua, Zengwu Shao, Shuhua Yang, Cao Yang
Accumulating evidence indicates that microRNAs can regulate the apoptosis of various cells. Apoptosis of nucleus pulposus cells plays an important role in the progression of intervertebral disc degeneration. The aim of this study is to investigate whether microRNA-143 (miRNA-143) is involved in the progression of intervertebral disc degeneration. In this study, the expression of miRNA-143 and its biological modulatory effects were examined. Messenger RNA and protein expression of miRNA-143 and B-cell lymphoma-2 (BCL2) in both normal and degenerative disc tissues was determined by using RT-PCR and western-blot assays...
July 14, 2017: Gene
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