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Chunli Song, Huanhuan Yang, Xiaochao Song, Deming Li, Xinli Li
OBJECTIVE: To investigate the effects of apple polyphenol on cell proliferation and migration of breast cancer cell line MDA-MB-231, and explore the potential mechanism. METHODS: The breast cancer cells in the logarithmic phase were treated with 0, 50, 100, 200, 400 and 800 μg/m L of apple polyphenol for 24, 48 and 72 h, then Trypan blue staining was employed to detect cell vitality; CCK8 kit was used to determine cell growth and proliferation; cell migration ability was observed by scratch experiment, and the change of proteins expression level was assessed by Western blot...
November 2017: Wei Sheng Yan Jiu, Journal of Hygiene Research
Debasis Patnaik, Pierre-Olivier Estève, Sriharsa Pradhan
Ubiquitin-like containing PHD Ring Finger 1 (UHRF1) is a multi-domain protein with a methyl-DNA binding SRA (SET and RING-associated) domain, required for maintenance DNA methylation mediated by DNMT1. Primarily expressed in proliferating cells, UHRF1 is a cell-cycle regulated protein that is required for S phase entry. Furthermore, UHRF1 participates in transcriptional gene regulation by connecting DNA methylation to histone modifications. Upregulation of UHRF1 may serve as a biomarker for a variety of cancers; including breast, gastric, prostate, lung and colorectal carcinoma...
May 25, 2018: Oncotarget
Yang Yang, Jing-Jing Pan, Xiao-Guang Zhou, Xiao-Yu Zhou, Rui Cheng
AIM: To reveal the role of miRNAs in retinopathy of prematurity (ROP) by bioinformatics analysis. METHODS: The raw data of this study came from the researches of Wang et al and Zhao et al who analyzed the microRNA (miRNA) expression profile between ROP and controls. Based on the identified differentially expressed miRNAs, the related target genes, lncRNA and circRNA were predicted. Then we performed functional enrichment analysis to further analyze the functions of target genes...
2018: International Journal of Ophthalmology
Naoya Murao, Shuzo Matsubara, Taito Matsuda, Hirofumi Noguchi, Tetsuji Mutoh, Masahiro Mutoh, Haruhiko Koseki, Masakazu Namihira, Kinichi Nakashima
Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis...
May 31, 2018: Neuroscience Research
Marilynn Chow, Lina Gao, Jason D MacManiman, Vincent T Bicocca, Bill H Chang, Joshi J Alumkal, Jeffrey W Tyner
Expression of the transmembrane pseudokinase ROR1 is required for survival of t(1;19)-pre-B-cell acute lymphoblastic leukemia (t(1;19) pre-B-ALL), chronic lymphocytic leukemia, and many solid tumors. However, targeting ROR1 with small-molecules has been challenging due to the absence of ROR1 kinase activity. To identify genes that regulate ROR1 expression and may, therefore, serve as surrogate drug targets, we employed an siRNA screening approach and determined that the epigenetic regulator and E3 ubiquitin ligase, UHRF1, is required for t(1;19) pre-B-ALL cell viability in a ROR1-dependent manner...
May 30, 2018: Oncogene
Bowen Yuan, Youhong Liu, Xiaohui Yu, Linglong Yin, Yuchong Peng, Yingxue Gao, Qianling Zhu, Tuoyu Cao, Yinke Yang, Xuegong Fan, Xiong Li
Therapy-induced expansion of cancer stem cells (CSCs) has been identified as one of the most critical factors contributing to therapeutic resistance, but the mechanisms of this adaptation are not fully understood. UHRF1 is a key epigenetic regulator responsible for therapeutic resistance, and controls the self-renewal of stem cells. In the present study, taxane-resistant cancer cells were established and stem-like cancer cells were expanded. UHRF1 was overexpressed in the taxane-resistant cancer cells, which maintained CSC characteristics...
May 11, 2018: Cell Death & Disease
Suman Abhishek, M Angel Nivya, Naveen Kumar Nakarakanti, Waghela Deeksha, Sanjeev Khosla, Eerappa Rajakumara
UHRF1 is a multi-domain protein comprising of a tandem tudor (UHRF1 TTD), a PHD finger, and a SET and RING-associated domain. It is required for the maintenance of CG methylation, heterochromatin formation and DNA repair. Isothermal titration calorimetry binding studies of unmodified and methylated lysine histone peptides establish that the UHRF1 TTD binds dimethylated Lys9 on histone H3 (H3K9me2). Further, MD simulation and binding studies reveal that TTD-PHD of UHRF1 (UHRF1 TTD-PHD) preferentially recognizes dimethyl-lysine status...
June 2018: Biochimie
Chuanyuan Wei, Nanhang Lu, Lu Wang, Yong Zhang, Zihao Feng, Yanwen Yang, Fazhi Qi, Jianying Gu
Melanoma is the most aggressive cutaneous cancer due to its propensity to metastasise and proliferate. Melanoma accounts for 80‑90% of skin‑cancer related deaths worldwide. Alhough numerous published studies have attempted to define the markers of diagnosis and prognosis of melanoma, a sensitive and specific biomarker for melanoma remains unknown. Recently, ubiquitin‑like with PHD and ring finger domains 1 (UHRF1) has attracted attention due to its role in cell proliferation and it has been deemed as a potential therapeutic target for cancer...
June 2018: Oncology Reports
Chao Chen, Sulan Zhai, Le Zhang, Jingjing Chen, Xuehui Long, Jun Qin, Jianhua Li, Ran Huo, Xiaoming Wang
The production of high-affinity antibody is essential for pathogen clearance. Antibody affinity is increased through germinal center (GC) affinity maturation, which relies on BCR somatic hypermutation (SHM) followed by antigen-based selection. GC B cell proliferation is essentially involved in these processes; it provides enough templates for SHM and also serves as a critical mechanism of positive selection. In this study, we show that expression of epigenetic regulator ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) was markedly up-regulated by c-Myc-AP4 in GC B cells, and it was required for GC response...
May 7, 2018: Journal of Experimental Medicine
Jang Hee Hong, Eun-Heui Jin, Soyeon Kim, Kyu-Sang Song, Jae Kyu Sung
DNA methylation is an important epigenetic modification that alters gene expression; DNA hypomethylation contributes to tumorigenesis through multiple processes. In the present study, the methylation of long interspersed element-1 (LINE-1) in 95 gastric cancer (GC) tissues and matched adjacent normal tissues was investigated by pyrosequencing. LINE-1 methylation was compared with the expression of ubiquitin-like with PHD and ring-finger protein 1 (UHRF1), an essential regulator of DNA methylation, using reverse transcription-quantitative polymerase chain reaction...
May 2018: Oncology Letters
Amir Ata Saei, Pierre Sabatier, Ülkü Güler Tokat, Alexey Chernobrovkin, Mohammad Pirmoradian, Roman A Zubarev
Chemotherapeutics cause the detachment and death of adherent cancer cells. When studying the proteome changes to determine the protein target and mechanism of action of anticancer drugs, the still-attached cells are normally used, while the detached cells are usually ignored. To test the hypothesis that proteomes of detached cells contain valuable information, we separately analyzed the proteomes of detached and attached HCT-116, A375 and RKO cells treated for 48 h with 5-fluorouracil, methotrexate and paclitaxel...
March 23, 2018: Molecular & Cellular Proteomics: MCP
Guillermo Senisterra, Hugh Y Zhu, Xiao Luo, Hailong Zhang, Guoliang Xun, Chunliang Lu, Wen Xiao, Taraneh Hajian, Peter Loppnau, Irene Chau, Fengling Li, Abdellah Allali-Hassani, Peter Atadja, Counde Oyang, En Li, Peter J Brown, Cheryl H Arrowsmith, Kehao Zhao, Zhengtian Yu, Masoud Vedadi
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a multidomain protein that plays a critical role in maintaining DNA methylation patterns through concurrent recognition of hemimethylated DNA and histone marks by various domains, and recruitment of DNA methyltransferase 1 (DNMT1). UHRF1 is overexpressed in various cancers, including breast cancer. The tandem tudor domain (TTD) of UHRF1 specifically and tightly binds to histone H3 di- or trimethylated at lysine 9 (H3K9me2 or H3K9me3, respectively), and this binding is essential for UHRF1 function...
March 1, 2018: SLAS Discovery
Leonardo Elia, Paolo Kunderfranco, Pierluigi Carullo, Marco Vacchiano, Floriana Maria Farina, Ignacio Fernando Hall, Stefano Mantero, Cristina Panico, Roberto Papait, Gianluigi Condorelli, Manuela Quintavalle
Adult vascular smooth muscle cells (VSMCs) dedifferentiate in response to extracellular cues such as vascular damage and inflammation. Dedifferentiated VSMCs are proliferative, migratory, less contractile, and can contribute to vascular repair as well as to cardiovascular pathologies such as intimal hyperplasia/restenosis in coronary artery and arterial aneurysm. We here demonstrate the role of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity...
May 7, 2018: Journal of Clinical Investigation
Saori Kataoka, Toshio Norikura, Shin Sato
Maternal malnutrition is known to increase the risk of obesity in offspring. We investigated whether green tea extract (GTE) intake during lactation affects obesity-related fibrosis and inflammation in the kidney of high-fat-diet-fed adult offspring of protein-restricted-diet-fed dams during pregnancy and lactation. Pregnant Wistar rats received diets containing 20% (normal-protein, NP) or 8% (low-protein, LP) casein, and they received 0%-, 0.12%- or 0.24%-GTE-containing LP diets (LP/LP, LP/LGT and LP/HGT, respectively) during lactation...
February 9, 2018: Journal of Nutritional Biochemistry
Jieying Chen, Xunan Sheng, Hongchang Ma, Zhengshan Tang, Chao Yang, Lanqin Cao, Yang Sun, Tanggang Deng, Peifu Feng, Bin Hu, Dong Wei, Jing Liu, Wei Xiong, Mao Ye
WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family characterized by the presence of a series of WD-repeat domains and is a scaffold protein that participates in telomerase assembly, Cajal body formation and DNA double strand break repair. Although previous studies have revealed that WDR79 is frequently overexpressed in non-small cell lung cancer (NSCLC) and promotes the proliferation of NSCLC cells, the underlying mechanism responsible for WDR79-mediated NSCLC proliferation is not fully understood...
May 2018: Journal of Cellular and Molecular Medicine
Alexander Beck, Franziska Trippel, Alexandra Wagner, Saskia Joppien, Max Felle, Christian Vokuhl, Thomas Schwarzmayr, Tim M Strom, Dietrich von Schweinitz, Gernot Längst, Roland Kappler
Background: Hepatoblastoma (HB) is the most common liver tumor of childhood and occurs predominantly within the first 3 years of life. In accordance to its early manifestation, HB has been described to display an extremely low mutation rate. As substitute, epigenetic modifiers seem to play an exceptional role in its tumorigenesis, which holds promise to develop targeted therapies and establish biomarkers for patient risk stratification. Results: We examined the role of a newly described protein complex consisting of three epigenetic regulators, namely E3 ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), ubiquitin-specific-processing protease 7 (USP7), and DNA methyltransferase 1 (DNMT1), in HB...
2018: Clinical Epigenetics
Robert M Vaughan, Bradley M Dickson, Evan M Cornett, Joseph S Harrison, Brian Kuhlman, Scott B Rothbart
UHRF1 is a histone- and DNA-binding E3 ubiquitin ligase that functions with DNMT1 to maintain mammalian DNA methylation. UHRF1 facilitates DNMT1 recruitment to replicating chromatin through a coordinated mechanism involving histone and DNA recognition and histone ubiquitination. UHRF2 shares structural homology with UHRF1, but surprisingly lacks functional redundancy to facilitate DNA methylation maintenance. Molecular mechanisms uncoupling UHRF2 from DNA methylation maintenance are poorly defined. Through comprehensive and comparative biochemical analysis of recombinant human UHRF1 and UHRF2 reader and writer activities, we reveal conserved modes of histone PTM recognition but divergent DNA binding properties...
February 28, 2018: Nucleic Acids Research
Tao Li, Linsheng Wang, Yongming Du, Si Xie, Xi Yang, Fuming Lian, Zhongjun Zhou, Chengmin Qian
UHRF1 plays multiple roles in regulating DNMT1-mediated DNA methylation maintenance during DNA replication. The UHRF1 C-terminal RING finger functions as an ubiquitin E3 ligase to establish histone H3 ubiquitination at Lys18 and/or Lys23, which is subsequently recognized by DNMT1 to promote its localization onto replication foci. Here, we present the crystal structure of DNMT1 RFTS domain in complex with ubiquitin and highlight a unique ubiquitin binding mode for the RFTS domain. We provide evidence that UHRF1 N-terminal ubiquitin-like domain (UBL) also binds directly to DNMT1...
April 6, 2018: Nucleic Acids Research
Elena Magnani, Filippo Macchi, Monica Mancini, Vanessa Lomazzi, Sara Cogliati, Christian Pistore, Martina Mandruzzato, Anne-Catherine Dock-Bregeon, Ian Marc Bonapace
Non-coding RNAs (ncRNAs) transcribed from the promoter and the downstream region can affect the expression of the corresponding coding genes. It has been shown that sense-directed ncRNAs arising from the promoter region of the E-cadherin gene (CDH1) mediate its repression. Here, we show that an antisense-directed ncRNA (paRCDH1-AS) transcribed from the CDH1 promoter is necessary for its expression. paRCDH1-AS acts as a hooking scaffold by recruiting the epigenetic regulators, UHRF1, DNMT3A, SUV39H1 and SUZ12, involved in CDH1 repression...
March 2018: Biochimica et Biophysica Acta
Eric Hervouet, Paul Peixoto, Régis Delage-Mourroux, Michaël Boyer-Guittaut, Pierre-François Cartron
Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes...
2018: Clinical Epigenetics
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