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https://www.readbyqxmd.com/read/28542928/crosstalk-between-e2f1-and-p53-transcription-factors-in-doxorubicin-induced-dna-damage-evidence-for-preventive-protective-effects-of-silymarin
#1
Seyedeh-Khadijeh Shafiei-Roudbari, Hassan Malekinejad, Hamed Janbaz-Aciabar, Mazdak Razi
OBJECTIVES: To study the effects of silymarin in various forms of applications on the molecular mechanism(s) of doxorubicin-induced testicular toxicity in male rats. METHODS: Following DOX administration with or without SMN in male rats, sperm quality assays were conducted. Moreover, total antioxidant capacity and nitric oxide content of testis were determined. Expression profile of p53 and E2F1 was analysed by PCR technique. Ultimately, the rate of DNA fragmentation in the testes was quantitatively measured...
May 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28542143/dna-damage-and-s-phase-dependent-e2f1-stabilization-requires-the-ciap1-e3-ubiquitin-ligase-and-is-associated-with-k63-poly-ubiquitination-on-lysine-161-164-residues
#2
Valérie Glorian, Jennifer Allègre, Jean Berthelet, Baptiste Dumetier, Pierre-Marie Boutanquoi, Nathalie Droin, Cémile Kayaci, Jessy Cartier, Simon Gemble, Guillaume Marcion, Daniel Gonzalez, Romain Boidot, Carmen Garrido, Olivier Michaud, Eric Solary, Laurence Dubrez
The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28515357/e2f1-inhibits-circulating-cholesterol-clearance-by-regulating-pcsk9-expression-in-the-liver
#3
Qiuwen Lai, Albert Giralt, Cédric Le May, Lianjun Zhang, Bertrand Cariou, Pierre-Damien Denechaud, Lluis Fajas
Cholesterol accumulation in the liver is an early event in nonalcoholic fatty liver disease (NAFLD). Here, we demonstrate that E2F1 plays a crucial role in maintaining cellular cholesterol homeostasis by regulating cholesterol uptake via proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme that promotes low-density lipoprotein receptor (LDLR) degradation upon activation. E2f1-/- mice display reduced total plasma cholesterol levels and increased cholesterol content in the liver. In this study, we show that E2f1 deletion in cellular and mouse models leads to a marked decrease in Pcsk9 expression and an increase in LDLR expression...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28511966/identification-of-potential-target-genes-and-related-regulatory-transcription-factors-in-spontaneous-hairline-fracture-induced-by-hypervitaminosis-a
#4
Chuangang Peng, Qi Yang, Bo Wei, Yong Liu, Yuxiang Li, Dawei Gu, Guochao Yin, Bo Wang, Dehui Xu, Xuebing Zhang, Daliang Kong
BACKGROUND: The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture. METHODS: The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken...
May 2, 2017: Injury
https://www.readbyqxmd.com/read/28504694/the-prohibitin-repressive-interaction-with-e2f1-is-rapidly-inhibited-by-androgen-signalling-in-prostate-cancer-cells
#5
S Koushyar, G Economides, S Zaat, W Jiang, C L Bevan, D A Dart
Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities across several cellular compartments including mitochondria, cell membrane and the nucleus. PHB and the steroid-activated androgen receptor (AR) have an interplay where AR downregulates PHB, and PHB represses AR. Additionally, their cellular locations and chromatin interactions are in dynamic opposition. We investigated the mechanisms of cell cycle inhibition by PHB and how this is modulated by AR in prostate cancer. Using a prostate cancer cell line overexpressing PHB, we analysed the gene expression changes associated with PHB-mediated cell cycle arrest...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28500630/e2f-is-involved-in-radioresistance-of-carbon-ion-induced-apoptosis-via-bax-caspase-3-signal-pathway-in-human-hepatoma-cell
#6
Xie Yi, S I Jing, Wang Yu-Pei, L I Hong-Yan, D I Cui-Xia, Yan Jun-Fang, Y E Yan-Cheng, Zhang Yan-Shan, Zhang Hong
Deletion of p53, most common genetic alteration, is observed in human tumors and reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR) could induce p53-/- cancer cells apoptosis. However, little is known regarding the molecular mechanism in this type of cell apoptosis. The present studies have focused on mechanisms state of signaling pathways as an activator of the cell fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up-regulation of E2F1 expression in cancer cells...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28498400/trim28-knockdown-increases-sensitivity-to-etoposide-by-upregulating-e2f1-in-non-small-cell-lung-cancer
#7
Lei Liu, Lijun Xiao, Xiujun Liang, Long Chen, Luyang Cheng, Lei Zhang, Xiaoguang Wu, Qian Xu, Chunhu Ma
Tripartite motif containing 28 (TRIM28) is a universal corepressor for Kruppel‑associated box zinc finger proteins. In our previous study, it was shown that expression of TRIM28 is upregulated in non‑small cell lung cancer (NSCLC) cell lines and tissues. Here, we demonstrated that the stable silencing of TRIM28 expression by a specific siRNA lentivirus vector increased the sensitivity of NSCLC cells to chemotherapeutic agent etoposide. Combination of TRIM28 siRNA and etoposide significantly inhibited the growth and proliferation of lung adenocarcinoma PAa cells and exerted obvious antitumor effects in nude mice...
May 11, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28494436/neuronal-tetraploidization-in-the-cerebral-cortex-correlates-with-reduced-cognition-in-mice-and-precedes-and-recapitulates-alzheimer-s-associated-neuropathology
#8
Noelia López-Sánchez, Ángela Fontán-Lozano, Anna Pallé, Valentina González-Álvarez, Alberto Rábano, José L Trejo, José M Frade
A controversy exists as to whether de novo-generated neuronal tetraploidy (dnNT) occurs in Alzheimer's disease. In addition, the presence of age-associated dnNT in the normal brain remains unexplored. Here we show that age-associated dnNT occurs in both superficial and deep layers of the cerebral cortex of adult mice, a process that is blocked in the absence of E2F1, a known regulator of cell cycle progression. This blockage correlates with improved cognition despite compromised neurogenesis in the adult hippocampus was confirmed in mice lacking the E2f1 gene...
April 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28489573/recombinant-sjp40-protein-enhances-p27-promoter-expression-in-hepatic-stellate-cells-via-an-e2f1-dependent-mechanism
#9
Yinong Duan, Lei Lyu, Dandan Zhu, Jianxin Wang, Jinling Chen, Liuting Chen, Chunzhao Yang, Xiaolei Sun
The p27 protein plays a critical role in cell cycle arrest. Our previous studies have demonstrated that recombinant P40 protein from Schistosoma japonicum (rSjP40) could induce G1 phase arrest of cell cycle. We, therefore, attempted to observe the effect of rSjP40 on p27 promoter activity in LX-2 cells and to explore its potential mechanisms in this study. Using both Western blot and dual-luciferase reporter assay, we demonstrated that rSjP40 could enhance the expression of p27 in LX-2 cells. Results obtained using truncated fragments of p27 promoter showed that rSjP40 increased p27 promoter activity in LX-2 cells, mainly via some transcription factors that bind to the -1740/-873 region of p27 promoter...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28485389/egfr-dependent-tor-independent-endocycles-support-drosophila-gut-epithelial-regeneration
#10
Jinyi Xiang, Jennifer Bandura, Peng Zhang, Yinhua Jin, Hanna Reuter, Bruce A Edgar
Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28484034/modeling-the-response-of-a-tumor-suppressive-network-to-mitogenic-and-oncogenic-signals
#11
Xinyu Tian, Bo Huang, Xiao-Peng Zhang, Mingyang Lu, Feng Liu, José N Onuchic, Wei Wang
Intrinsic tumor-suppressive mechanisms protect normal cells against aberrant proliferation. Although cellular signaling pathways engaged in tumor repression have been largely identified, how they are orchestrated to fulfill their function still remains elusive. Here, we built a tumor-suppressive network model composed of three modules responsible for the regulation of cell proliferation, activation of p53, and induction of apoptosis. Numerical simulations show a rich repertoire of network dynamics when normal cells are subject to serum stimulation and adenovirus E1A overexpression...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28481029/loss-of-h2b-monoubiquitination-is-associated-with-poor-differentiation-and-enhanced-malignancy-of-lung-adenocarcinoma
#12
Keqiang Zhang, Jinhui Wang, Tommy R Tong, Xiwei Wu, Rebecca Nelson, Yate-Ching Yuan, Theresa Reno, Zheng Liu, Xinwei Yun, Jae Y Kim, Ravi Salgia, Dan J Raz
Deregulated monoubiquitination of histone H2B (H2Bub1), mainly catalyzed by E3 ubiquitin-protein ligase RNF20/RNF40 complex, may play an important role in cancer. Here we investigate potential roles of H2Bub1 and the underlying mechanisms through which it contributes to cancer development and progression in lung adenocarcinoma. We show that downregulation of H2Bub1 through RNF20 knockdown dramatically decreases H3K79 and H3K4 trimethylation in both normal and malignant lung epithelial cell lines. Concurrently, global transcriptional profiling analysis reveals that multiple tumor-associated genes such as CCND3, E2F1/2, HOXA1, Bcl2 modifying factor (BMF), Met, and Myc; and signaling pathways of cellular dedifferentiation, proliferation, adhesion, survival including p53, cadherin, Myc, and anti-apoptotic pathways are differentially expressed or significantly altered in these lung epithelial cells upon downregulation of H2Bub1...
May 8, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28477016/e6ap-promotes-prostate-cancer-by-reducing-p27-expression
#13
Dinesh Raghu, Piotr Jan Paul, Twishi Gulati, Siddhartha Deb, Christine Khoo, Andrea Russo, Enzo Gallo, Giovanni Blandino, Ai-Leen Chan, Elena Takano, Shahneen K Sandhu, Stephen B Fox, Scott Williams, Sue Haupt, Cristina Gamell, Ygal Haupt
Prostate cancer (PC) is the most common cancer in men. Elevated levels of E3 ligase, E6-Associated Protein (E6AP) were previously linked to PC, consistent with increased protein expression in a subset of PC patients. In cancers, irregular E3 ligase activity drives proteasomal degradation of tumor suppressor proteins. Accordingly, E3 ligase inhibitors define a rational therapy to restore tumor suppression. The relevant tumor suppressors targeted by E6AP in PC are yet to be fully identified. In this study we show that p27, a key cell cycle regulator, is a target of E6AP in PC...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28474358/e2f1interactive-with-brca1-pathway-induces-hcc-two-different-small-molecule-metabolism-or-cell-cycle-regulation-via-mitochondrion-or-cd4-t-to-cytosol
#14
Qingchun Chen, Lin Wang, Minghu Jiang, Juxiang Huang, Zhenfu Jiang, Haitao Feng, Zhili Ji
Breast cancer 1 (BRCA1) and E2F transcription factor 1 (E2F1) are related to metabolism and cell cycle regulation. However, the corresponding mechanism is not clear in HCC. High BRCA1 direct pathway was constructed with 11 molecules from E2F1 feedback-interactive network in HCC by GRNInfer based on 39 Pearson mutual positive corelation CC >0.25 molecules with E2F1. Integration of GRNInfer with GO, KEGG, BioCarta, GNF_U133A, UNIGENE_EST, Disease, GenMAPP databases by DAVID and MAS 3.0, E2F1 feedback-interactive BRCA1 indirect mitochondrion to cytosol pathway was identified as upstream LAPTM4B activation, feedback UNG, downstream BCAT1-HIST1H2AD-TK1 reflecting protein and DNA binding with enrichment of small molecule metabolism; The corresponding BRCA1 indirect membrane to cytosol pathway as upstream CCNB2-NUSAP1 activation, feedback TTK-HIST1H2BJ-CENPF, downstream MCM4-TK1 reflecting ATP and microtubule binding with enrichment of CD4+T-related cell cycle regulation in HCC...
May 5, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28467792/assessment-of-citalopram-and-escitalopram-on-neuroblastoma-cell-lines-cell-toxicity-and-gene-modulation
#15
Laurent Sakka, Nathalie Delétage, Maryse Chalus, Youssef Aissouni, Valérie Sylvain-Vidal, Stéphane Gobron, Guillaume Coll
Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28464886/a-lung-cancer-risk-classifier-comprising-genome-maintenance-genes-measured-in-normal-bronchial-epithelial-cells
#16
Jiyoun Yeo, Erin L Crawford, Xiaolu Zhang, Sadik Khuder, Tian Chen, Albert Levin, Thomas M Blomquist, James C Willey
BACKGROUND: Annual low dose CT (LDCT) screening of individuals at high demographic risk reduces lung cancer mortality by more than 20%. However, subjects selected for screening based on demographic criteria typically have less than a 10% lifetime risk for lung cancer. Thus, there is need for a biomarker that better stratifies subjects for LDCT screening. Toward this goal, we previously reported a lung cancer risk test (LCRT) biomarker comprising 14 genome-maintenance (GM) pathway genes measured in normal bronchial epithelial cells (NBEC) that accurately classified cancer (CA) from non-cancer (NC) subjects...
May 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28446478/correction-to-telomerase-reverse-transcriptase-deficiency-prevents-neointima-formation-through-chromatin-silencing-of-e2f1-target-genes
#17
(no author information available yet)
No abstract text is available yet for this article.
May 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28429752/lncrna-hit-promotes-cell-proliferation-of-non-small-cell-lung-cancer-by-association-with-e2f1
#18
L Yu, F Fang, S Lu, X Li, Y Yang, Z Wang
Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively...
May 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28427185/transcriptional-landscape-of-human-cancers
#19
Mengyuan Li, Qingrong Sun, Xiaosheng Wang
The homogeneity and heterogeneity in somatic mutations, copy number alterations and methylation across different cancer types have been extensively explored. However, the related exploration based on transcriptome data is lacking. In this study we explored gene expression profiles across 33 human cancer types using The Cancer Genome Atlas (TCGA) data. We identified consistently upregulated genes (such as E2F1, EZH2, FOXM1, MYBL2, PLK1, TTK, AURKA/B and BUB1) and consistently downregulated genes (such as SCARA5, MYOM1, NKAPL, PEG3, USP2, SLC5A7 and HMGCLL1) across various cancers...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423669/the-novel-long-non-coding-rna-talnec2-regulates-tumor-cell-growth-and-the-stemness-and-radiation-response-of-glioma-stem-cells
#20
Shlomit Brodie, Hae Kyung Lee, Wei Jiang, Simona Cazacu, Cunli Xiang, Laila M Poisson, Indrani Datta, Steve Kalkanis, Doron Ginsberg, Chaya Brodie
Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need to identify molecular mechanisms that play a role in patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM with poor prognosis, in GBM specimens derived from short-term survivors and in glioma cells and glioma stem cells (GSCs)...
May 9, 2017: Oncotarget
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