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https://www.readbyqxmd.com/read/29452418/phf20-collaborates-with-parp1-to-promote-stemness-and-aggressiveness-of-neuroblastoma-cells-through-activation-of-sox2-and-oct4
#1
Wenyong Long, Wei Zhao, Bo Ning, Jing Huang, Junjun Chu, Linfeng Li, Qianquan Ma, Changsheng Xing, Helen Y Wang, Qing Liu, Rong-Fu Wang
The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of stemness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Cas9-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. Expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients...
February 14, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29447383/super-resolution-imaging-identifies-parp1-and-the-ku-complex-acting-as-dna-double-strand-break-sensors
#2
Guang Yang, Chao Liu, Shih-Hsun Chen, Muzaffer A Kassab, J Damon Hoff, Nils G Walter, Xiaochun Yu
DNA double-strand breaks (DSBs) are fatal DNA lesions and activate a rapid DNA damage response. However, the earliest stage of DSB sensing remains elusive. Here, we report that PARP1 and the Ku70/80 complex localize to DNA lesions considerably earlier than other DSB sensors. Using super-resolved fluorescent particle tracking, we further examine the relocation kinetics of PARP1 and the Ku70/80 complex to a single DSB, and find that PARP1 and the Ku70/80 complex are recruited to the DSB almost at the same time...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29445424/promoter-methylation-of-dna-damage-repair-ddr-genes-in-human-tumor-entities-rbbp8-ctip-is-almost-exclusively-methylated-in-bladder-cancer
#3
Jolein Mijnes, Jürgen Veeck, Nadine T Gaisa, Eduard Burghardt, Tim C de Ruijter, Sonja Gostek, Edgar Dahl, David Pfister, Sebastian C Schmid, Ruth Knüchel, Michael Rose
Background: Genome-wide studies identified pan-cancer genes and shared biological networks affected by epigenetic dysregulation among diverse tumor entities. Here, we systematically screened for hypermethylation of DNA damage repair (DDR) genes in a comprehensive candidate-approach and exemplarily identify and validate candidate DDR genes as targets of epigenetic inactivation unique to bladder cancer (BLCA), which may serve as non-invasive biomarkers. Methods: Genome-wide DNA methylation datasets (2755 CpG probes of n = 7819 tumor and n = 659 normal samples) of the TCGA network covering 32 tumor entities were analyzed in silico for 177 DDR genes...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29442331/role-of-zic-family-proteins-in-transcriptional-regulation-and-chromatin-remodeling
#4
Minoru Hatayama, Jun Aruga
Proper functions of Zic proteins are essential for animals in health and disease. Here, we summarize our current understanding of the molecular properties and functions of the Zic family across animal species and paralog subtypes. Zics are basic proteins with some posttranslational modifications and can move to the cell nucleus via importin- and CRM1-based nucleocytoplasmic shuttling mechanisms. Degradation is mediated by the ubiquitin proteasome system. Many Zic proteins are capable of binding to two types of target DNA sequences (CTGCTG-core-type and GC-stretch-type)...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29433299/cocoplum-chrysobalanus-icaco-l-decreases-doxorubicin-induced-dna-damage-and-downregulates-gadd45a-il-1%C3%AE-and-tnf-%C3%AE-in-vivo
#5
Vinicius Paula Venancio, Mara Ribeiro Almeida, Lusânia Maria Greggi Antunes
DNA damage and inflammation are promising targets in disease prevention studies. Since these pathways have shown to be modulated by dietary components, investigating the molecular effects of food becomes relevant. This study aimed at investigating the protective effects of cocoplum (Chrysobalanus icaco L.) against doxorubicin (DXR)-induced damage. Rats were treated with cocoplum (100, 200 or 400mg/kg/day) for 14days, associated or not with DXR (15mg/kg b.w.). Tissue-targeted comet assay and the oxidative stress parameters oxidized/reduced glutathione and catalase were investigated in liver, kidney, and heart...
March 2018: Food Research International
https://www.readbyqxmd.com/read/29429513/protective-roles-of-rutin-against-restraint-stress-on-spermatogenesis-in-testes-of-adult-mice
#6
Asif Mehfooz, Quanwei Wei, Kaizhi Zheng, Mohamed Babo Fadlalla, Gracijela Maltasic, Fangxiong Shi
In order to investigate the effects of Rutin against restraint stress, 50 adult male mice were divided into five groups: control, restraint stress (RS), and RS with 2 doses of Rutin treatments. Mice were restrained in a conical tube for 4 h daily and Rutin was injected intraperitoneally for 15 consecutive days. Restraint stress significantly decreases body weights, testis and epididymis weights, thymus weights, visceral fats, serum concentrations of testosterone, sperm counts, sperm motility and sperm viability, while it increases serum epinephrine levels, adrenal gland weights and abnormal sperms...
February 2018: Tissue & Cell
https://www.readbyqxmd.com/read/29428961/itraq-based-proteomics-analysis-of-triptolide-on-human-a549-lung-adenocarcinoma-cells
#7
Fangqiong Li, Dongxiao Zhao, Suwen Yang, Juan Wang, Qin Liu, Xin Jin, Wei Wang
BACKGROUND/AIMS: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood...
February 2, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29423093/combination-of-a-hypomethylating-agent-and-inhibitors-of-parp-and-hdac-traps-parp1-and-dnmt1-to-chromatin-acetylates-dna-repair-proteins-down-regulates-nurd-and-induces-apoptosis-in-human-leukemia-and-lymphoma-cells
#8
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
Combination of drugs that target different aspects of aberrant cellular processes is an efficacious treatment for hematological malignancies. Hypomethylating agents (HMAs) and inhibitors of poly(ADP-ribose) polymerases (PARPis) and histone deacetylases (HDACis) are clinically active anti-tumor drugs. We hypothesized that their combination would be synergistically cytotoxic to leukemia and lymphoma cells. Exposure of AML and lymphoma cell lines to the combination of the PARPi niraparib (Npb), the HMA decitabine (DAC) and the HDACi romidepsin (Rom) or panobinostat (Pano) synergistically inhibited cell proliferation by up to 70% via activation of the ATM pathway, increased production of reactive oxygen species, decreased mitochondrial membrane potential, and activated apoptosis...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29408941/chromatin-remodeler-alc1-prevents-replication-fork-collapse-by-slowing-fork-progression
#9
Masato Ooka, Takuya Abe, Kosai Cho, Kaoru Koike, Shunichi Takeda, Kouji Hirota
ALC1 (amplified in liver cancer 1), an SNF2 superfamily chromatin-remodeling factor also known as CHD1L (chromodomain helicase/ATPase DNA binding protein 1-like), is implicated in base-excision repair, where PARP (Poly(ADP-ribose) polymerase) mediated Poly(ADP-ribose) signaling facilitates the recruitment of this protein to damage sites. We here demonstrate the critical role played by ALC1 in the regulation of replication-fork progression in cleaved template strands. To analyze the role played by ALC1 as well as its functional relationship with PARP1, we generated ALC1-/-, PARP1-/-, and ALC1-/-/PARP1-/- cells from chicken DT40 cells...
2018: PloS One
https://www.readbyqxmd.com/read/29405820/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-parp1-inhibitor-niraparib-to-kill-ovarian-cancer-cells
#10
Laurence Booth, Jane L Roberts, Peter Samuel, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor neratinib has been shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET, PDGFRα and mutant RAS proteins via autophagic degradation. Neratinib interacted in an additive to synergistic fashion with the approved PARP1 inhibitor niraparib to kill ovarian cancer cells. Neratinib and niraparib caused the ATM-dependent activation of AMPK which in turn was required to cause mTOR inactivation, ULK-1 activation and ATG13 phosphorylation. The drug combination initially increased autophagosome levels followed later by autolysosome levels...
February 6, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29398669/anti-inflammatory-effect-of-tranexamic-acid-against-trauma-hemorrhagic-shock-induced-acute-lung-injury-in-rats
#11
Yue Teng, Cong Feng, Yunen Liu, Hongxu Jin, Yan Gao, Tanshi Li
It has been demonstrated that tranexamic acid (TXA), a synthetic derivative of lysine, alleviates lung damage in a trauma-hemorrhagic shock (T/HS) model. Nevertheless, the mechanism of TXA against acute lung injury (ALI) has not deeply elaborated. In this study, we generated a T/HS rat model based on previous research, and TXA (50 mg/kg and 100 mg/kg) was intravenously injected into these rats prior to or post T/HS. The results revealed that the decreased survival rate and impaired lung permeability of the rats caused by T/HS were improved by TXA pretreatment or posttreatment...
February 2, 2018: Experimental Animals
https://www.readbyqxmd.com/read/29398485/risk-associated-long-noncoding-rna-foxd3-as1-inhibits-neuroblastoma-progression-by-repressing-parp1-mediated-activation-of-ctcf
#12
Xiang Zhao, Dan Li, Dandan Huang, Huajie Song, Hong Mei, Erhu Fang, Xiaojing Wang, Feng Yang, Liduan Zheng, Kai Huang, Qiangsong Tong
Neuroblastoma (NB) is the most common extracranial tumor in childhood. Recent studies have implicated the emerging roles of long noncoding RNAs (lncRNAs) in tumorigenesis and aggressiveness. However, the functions and targets of risk-associated lncRNAs in NB progression still remain to be determined. Herein, through mining of public microarray datasets, we identify lncRNA forkhead box D3 antisense RNA 1 (FOXD3-AS1) as an independent prognostic marker for favorable outcome of NB patients. FOXD3-AS1 is downregulated in NB tissues and cell lines, and ectopic expression of FOXD3-AS1 induces neuronal differentiation and decreases the aggressiveness of NB cells in vitro and in vivo...
December 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29393407/parp1-sirna-suppresses-human-prostate-cancer-cell-growth-and-progression
#13
Yongchang Lai, Zhenzhen Kong, Tao Zeng, Shaohong Xu, Xiaolu Duan, Shujue Li, Chao Cai, Zhijian Zhao, Wenqi Wu
Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib or rucaparib, have shown treatment efficacy in BRCA1/2-deficient tumors. However, since PARP inhibitors (PARPi) mainly modulate the activation of PARP but not its expression, whether small interfering RNA (siRNA) specific to PARP has the same function as PARPi has not been well defined. In the present study it was demonstrated that PARP1-siRNA could reduce prostate cancer (PCa) cell progression regardless of the BRCA1/2 mutation. PARP1 silencing could significantly inhibit PC3 cell migration and invasion...
January 26, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29371919/sensitizing-ewing-sarcoma-to-chemo-and-radiotherapy-by-inhibition-of-the-dna-repair-enzymes-dna-protein-kinase-dna-pk-and-poly-adp-ribose-polymerase-parp-1-2
#14
Britta Vormoor, Yvonne T Schlosser, Helen Blair, Abhishek Sharma, Sarah Wilkinson, David R Newell, Nicola Curtin
Background: DNA-PK and PARP inhibitors sensitize cancer cells to chemo- and radiotherapy. ETS transcription factors (EWS-FLI1) have been described as biomarkers for PARP-inhibitor sensitivity. Sensitivity to single agent PARP inhibitors has so far been limited to homologous recombination repair (HRR) deficient tumors, exploiting synthetic lethality. Results: In clonogenic assays, single agent rucaparib LD50 values for continuously exposed cells were similar to those observed in HRR-defective cells (CAPAN-1 cell line, BRCA2 defective); however, both ES cell lines (TC-71, CADO-ES1) had functional HRR...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29367615/microrna-379-5p-is-associate-with-biochemical-premature-ovarian-insufficiency-through-parp1-and-xrcc6
#15
Yujie Dang, Xiaoyan Wang, Yajing Hao, Xinyue Zhang, Shidou Zhao, Jinlong Ma, Yingying Qin, Zi-Jiang Chen
Premature ovarian insufficiency (POI) imposes great challenges on women's fertility and lifelong health. POI is highly heterogeneous and encompasses occult, biochemical, and overt stages. MicroRNAs (miRNAs) are negative regulators of gene expression, whose roles in physiology and diseases like cancers and neurological disorders have been recognized, but little is known about the miRNAs profile and functional relevance in biochemical POI (bPOI). In this study, the expression of miRNAs and mRNAs in granulosa cells (GCs) of bPOI women was determined by two microarrays, respectively...
January 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29366480/septin4-as-a-novel-binding-partner-of-parp1-contributes-to-oxidative-stress-induced-human-umbilical-vein-endothelial-cells-injure
#16
Naijin Zhang, Ying Zhang, Sichao Zhao, Yingxian Sun
Oxidative stress induced vascular endothelial cell injure is one of the key and initial event in the development of atherosclerosis. Septin4, as a member of GTP binding protein family, is widely expressed in the eukaryotic cells and considered to be an essential component of the cytoskeleton which is involved in many important physiological processes. However, whether Septin4 is involved in cardiovascular diseases, such as oxidative stress inducted endothelial cell injury still unclear. PARP1 as a DNA repair enzyme can be activated by identifying DNA damaged fragments, which consumes high levels of energy and leads to vascular endothelial cell apoptosis...
January 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29361132/characterization-of-dna-adp-ribosyltransferase-activities-of-parp2-and-parp3-new-insights-into-dna-adp-ribosylation
#17
Gabriella Zarkovic, Ekaterina A Belousova, Ibtissam Talhaoui, Christine Saint-Pierre, Mikhail M Kutuzov, Bakhyt T Matkarimov, Denis Biard, Didier Gasparutto, Olga I Lavrik, Alexander A Ishchenko
Poly(ADP-ribose) polymerases (PARPs) act as DNA break sensors and catalyze the synthesis of polymers of ADP-ribose (PAR) covalently attached to acceptor proteins at DNA damage sites. It has been demonstrated that both mammalian PARP1 and PARP2 PARylate double-strand break termini in DNA oligonucleotide duplexes in vitro. Here, we show that mammalian PARP2 and PARP3 can PARylate and mono(ADP-ribosyl)ate (MARylate), respectively, 5'- and 3'-terminal phosphate residues at double- and single-strand break termini of a DNA molecule containing multiple strand breaks...
January 18, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29356242/preferable-in-vitro-condition-for-maintaining-faithful-dna-methylation-imprinting-in-mouse-embryonic-stem-cells
#18
Jiyoung Lee, Ayumi Matsuzawa, Hirosuke Shiura, Akito Sutani, Fumitoshi Ishino
Epigenetic properties of cultured embryonic stem cells (ESCs), including DNA methylation imprinting, are important because they affect the developmental potential. Here, we tested a variety of culture media, including knockout serum replacement (KSR) and fetal bovine serum (FBS) with or without inhibitors of Gsk3β and Mek1/2 (2i) at various time points. In addition to the previously known passage-dependent global changes, unexpected dynamic DNA methylation changes occurred in both maternal and paternal differentially methylated regions: under the widely used condition of KSR with 2i, a highly hypomethylated state occurred at early passages (P1-7) as well as P10, but DNA methylation increased over further passages in most conditions, except under KSR with 2i at P25...
January 22, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29348879/loss-of-neil3-dna-glycosylase-markedly-increases-replication-associated-double-strand-breaks-and-enhances-sensitivity-to-atr-inhibitor-in-glioblastoma-cells
#19
Alex W Klattenhoff, Megha Thakur, Christopher S Chu, Debolina Ray, Samy L Habib, Dawit Kidane
DNA endonuclease eight-like glycosylase 3 (NEIL3) is one of the DNA glycosylases that removes oxidized DNA base lesions from single-stranded DNA (ssDNA) and non-B DNA structures. Approximately seven percent of human tumors have an altered NEIL3 gene. However, the role of NEIL3 in replication-associated repair and its impact on modulating treatment response is not known. Here, we report that NEIL3 is localized at the DNA double-strand break (DSB) sites during oxidative DNA damage and replication stress. Loss of NEIL3 significantly increased spontaneous replication-associated DSBs and recruitment of replication protein A (RPA)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29343717/the-role-of-nf%C3%AE%C2%BAb-in-spheroid-formation-of-human-breast-cancer-cells-cultured-on-the-random-positioning-machine
#20
Sascha Kopp, Jayashree Sahana, Tawhidul Islam, Asbjørn Graver Petersen, Johann Bauer, Thomas J Corydon, Herbert Schulz, Kathrin Saar, Norbert Huebner, Lasse Slumstrup, Stefan Riwaldt, Markus Wehland, Manfred Infanger, Ronald Luetzenberg, Daniela Grimm
Human MCF-7 breast cancer cells were exposed to a Random Positioning Machine (RPM). After 24 hours (h) the cells grew either adherently within a monolayer (AD) or within multicellular spheroids (MCS). AD and MCS populations were separately harvested, their cellular differences were determined performing qPCR on genes, which were differently expressed in AD and MCS cells. Gene array technology was applied to detect RPM-sensitive genes in MCF-7 cells after 24 h. Furthermore, the capability to form multicellular spheroids in vitro was compared with the intracellular distribution of NF-kappaB (NFκB) p65...
January 17, 2018: Scientific Reports
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