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https://www.readbyqxmd.com/read/28812991/the-retinoblastoma-rb-tumor-suppressor-pushing-back-against-genome-instability-on-multiple-fronts
#1
REVIEW
Renier Vélez-Cruz, David G Johnson
The retinoblastoma (RB) tumor suppressor is known as a master regulator of the cell cycle. RB is mutated or functionally inactivated in the majority of human cancers. This transcriptional regulator exerts its function in cell cycle control through its interaction with the E2F family of transcription factors and with chromatin remodelers and modifiers that contribute to the repression of genes important for cell cycle progression. Over the years, studies have shown that RB participates in multiple processes in addition to cell cycle control...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#2
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28806394/smggds-is-a-transient-nucleolar-protein-that-protects-cells-from-nucleolar-stress-and-promotes-the-cell-cycle-by-regulating-dream-complex-gene-expression
#3
P Gonyo, C Bergom, A C Brandt, S-W Tsaih, Y Sun, T M Bigley, E L Lorimer, S S Terhune, H Rui, M J Flister, R M Long, C L Williams
The chaperone protein and guanine nucleotide exchange factor SmgGDS (RAP1GDS1) is a key promoter of cancer cell proliferation and tumorigenesis. SmgGDS undergoes nucleocytoplasmic shuttling, suggesting that it has both cytoplasmic and nuclear functions that promote cancer. Previous studies indicate that SmgGDS binds cytoplasmic small GTPases and promotes their trafficking to the plasma membrane. In contrast, little is known about the functions of SmgGDS in the nucleus, or how these nuclear functions might benefit cancer cells...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28797284/gambogic-acid-sensitizes-gemcitabine-efficacy-in-pancreatic-cancer-by-reducing-the-expression-of-ribonucleotide-reductase-subunit-m2-rrm2
#4
Guanggai Xia, Hongcheng Wang, Ziliang Song, Qingcai Meng, Xiuyan Huang, Xinyu Huang
BACKGROUND: Pancreatic cancer is susceptible to gemcitabine resistance, and patients receive less benefit from gemcitabine chemotherapy. Previous studies report that gambogic acid possesses antineoplastic properties; however, to our knowledge, there have been no specific studies on its effects in pancreatic cancer. Therefore, the purpose of this study was to explore whether increases the sensitivity of pancreatic cancer to gemcitabine, and determine the synergistic effects of gambogic acid and gemcitabine against pancreatic cancer...
August 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28797103/effects-of-cancer-testis-antigen-tfdp3-on-cell-cycle-regulation-and-its-mechanism-in-l-02-and-hepg2-cell-lines-in-vitro
#5
Yunshen Jiao, Lingyu Ding, Ming Chu, Tieshan Wang, Jiarui Kang, Xiaofan Zhao, Huanhuan Li, Xi Chen, Zirui Gao, Likai Gao, Yuedan Wang
TFDP3, also be known as HCA661, was one of the cancer-testis antigens, which only expressed in human tissues. The recent researches about TFDP3 mostly focused on its ability to control the drug resistance and apoptosis of tumor cells. However, the role of TFDP3 in the progress of the cell cycle is rarely involved. In this study, we examined the expression of TFDP3 in human liver tissues firstly. After that, we detect the expression of TFDP3 at the RNA level and protein level in L-02 cell line and HepG2 cell line, and the location of TFDP3 was defined by immunofluorescence technique...
2017: PloS One
https://www.readbyqxmd.com/read/28794159/p63%C3%AE-protein-upregulates-heat-shock-protein-70-expression-via-e2f1-transcription-factor-1-promoting-wasf3-wave3-mmp9-signaling-and-bladder-cancer-invasion
#6
Honglei Jin, Qipeng Xie, Xirui Guo, Jiheng Xu, Annette Wang, Jingxia Li, Junlan Zhu, Xue-Ru Wu, Haishan Huang, Chuanshu Huang
Bladder cancer (BC) is the sixth most common cancer in the United States and is the number one cause of death among patients with urinary system malignancies. This makes the identification of invasive regulator(s)/effector(s) as the potential therapeutic targets for managing BC a high priority. p63 is a member of the p53 family of tumor suppressor genes/proteins, plays a role in the differentiation of epithelial tissues, and is believed to function as a tumor suppressor. However, whether and how p63 functions in BC cell invasion after tumorigenesis remains unclear...
August 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28775339/unraveling-a-tumor-type-specific-regulatory-core-underlying-e2f1-mediated-epithelial-mesenchymal-transition-to-predict-receptor-protein-signatures
#7
Faiz M Khan, Stephan Marquardt, Shailendra K Gupta, Susanne Knoll, Ulf Schmitz, Alf Spitschak, David Engelmann, Julio Vera, Olaf Wolkenhauer, Brigitte M Pützer
Cancer is a disease of subverted regulatory pathways. In this paper, we reconstruct the regulatory network around E2F, a family of transcription factors whose deregulation has been associated to cancer progression, chemoresistance, invasiveness, and metastasis. We integrate gene expression profiles of cancer cell lines from two E2F1-driven highly aggressive bladder and breast tumors, and use network analysis methods to identify the tumor type-specific core of the network. By combining logic-based network modeling, in vitro experimentation, and gene expression profiles from patient cohorts displaying tumor aggressiveness, we identify and experimentally validate distinctive, tumor type-specific signatures of receptor proteins associated to epithelial-mesenchymal transition in bladder and breast cancer...
August 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28753861/e2f1-signalling-is-predictive-of-chemoresistance-and-lymphogenic-metastasis-in-penile-cancer-a-pilot-functional-study-reveals-new-prognostic-biomarkers
#8
Ferdinand Fenner, Deborah Goody, Chris Protzel, Andreas Erbersdobler, Christin Richter, Juliane M Hartz, Carsten M Naumann, Holger Kalthoff, Ottmar Herchenröder, Oliver W Hakenberg, Brigitte M Pützer
BACKGROUND: For penile cancer (PC) there are no known molecular predictors of lymphatic spread and/or chemoresistance. OBJECTIVE: To identify functional biomarkers that can predict malignant progression and treatment responsiveness. DESIGN, SETTING, AND PARTICIPANTS: We used four patient-derived PC cell lines and measured invasion and capillary tube formation, chemoresponsiveness, and mRNA and protein expression. Data were further validated in E2F1 transcription factor knockdown and overexpression experiments...
March 1, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28751617/cdk4-6-inhibition-is-more-active-against-the-glioblastoma-proneural-subtype
#9
Ming Li, Aizhen Xiao, Desiree Floyd, Inan Olmez, Jeongwu Lee, Jakub Godlewski, Agnieszka Bronisz, Krishna P L Bhat, Erik P Sulman, Ichiro Nakano, Benjamin Purow
Glioblastoma (GBM) is the most common and lethal brain tumor. Gene expression profiling has classified GBM into distinct subtypes, including proneural, mesenchymal, and classical, and identifying therapeutic vulnerabilities of these subtypes is an extremely high priority. We leveraged The Cancer Genome Atlas (TCGA) data, in particular for microRNA expression, to seek druggable core pathways in GBM. The E2F1-regulated miR-17~92 cluster and its analogs are shown to be highly expressed in proneural GBM and in GSC lines, suggesting the E2F cell cycle pathway might be a key driver in proneural GBM...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28745544/euptox-a-induces-g1-arrest-and-autophagy-via-p38-mapk-and-pi3k-akt-mtor-mediated-pathways-in-mouse-splenocytes
#10
Quan Mo, Liwen Hu, Jiahua Weng, Yong Zhang, Yancheng Zhou, Ruiguang Xu, Zhicai Zuo, Junliang Deng, Zhihua Ren, Zhijun Zhong, Guangneng Peng, Xiang Nong, Yahui Wei, Yanchun Hu
Euptox A (9-oxo-10, 11-dehydroageraphorone), the main toxin isolated from Eupatorium adenophorum, is known to induce immunotoxicity in animals. However, the precise mechanism underlying the effects of Euptox A on splenocytes is unclear. Here, we aimed to investigate the molecular mechanisms underlying the effect of Euptox A in mouse spleens after its intragastric administration and found that Euptox A exhibits proautophagic effects in splenocytes. Euptox A markedly arrested the splenocytes in the G0/G1 phase, which was accompanied by inhibition of the expression of the positive regulators CDK4, CDK2, cyclin D1, PCNA, and E2F1, and promotion of the expression of the negative regulators p53, p21 Waf1/Cip1, p27 Kip1, and Chk1...
July 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28740578/clinical-performance-of-e2fs-1-3-in-kidney-clear-cell-renal-cancer-evidence-from-bioinformatics-analysis
#11
Bin Liang, Jianying Zhao, Xuan Wang
Extensive research on the E2F transcription factor family has led to numerous insights that E2Fs were involved not only in proliferation and tumorigenesis but also in apoptosis and differentiation. In the present study, we analyzed the differential expression of E2Fs1-3 genes, and also evaluated the impact of E2Fs 1-3 genes expression on clinical outcome from the Cancer Genome Atlas (TCGA) database. The results showed that E2F1, E2F2 and E2F3 expression was increased in KIRC tissues than matched normal tissues (E2F1, P < 0...
May 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28730077/proteomic-profiling-of-early-degenerative-retina-of-rcs-rats
#12
Zhi-Hong Zhu, Yan Fu, Chuan-Huang Weng, Cong-Jian Zhao, Zheng-Qin Yin
AIM: To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). METHODS: Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs)...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28723554/hypoxia-sensitive-commd1-integrates-signaling-and-cellular-metabolism-in-human-macrophages-and-suppresses-osteoclastogenesis
#13
Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723239/disruption-of-cdk-resistant-chromatin-association-by-prb-causes-dna-damage-mitotic-errors-and-reduces-condensin-ii-recruitment
#14
Charles A Ishak, Courtney H Coschi, Michael V Roes, Frederick A Dick
Organization of chromatin structure is indispensible to the maintenance of genome integrity. The retinoblastoma tumor suppressor protein (pRB) mediates both transcriptional repression and chromatin organization, but the independent contributions of these functions have been difficult to study. Here, we utilize a synthetic Rb1 mutant allele (F832A) that maintains pRB association at cell cycle gene promoters, but disrupts a cyclin-dependent kinase (CDK)-resistant interaction with E2F1 to reduce occupancy of pRB on intergenic chromatin...
August 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28721074/targeted-regulation-of-mir-98-on-e2f1-increases-chemosensitivity-of-leukemia-cells-k562-a02
#15
Yingdan Huang, Xiuli Hong, Jiasheng Hu, Quanyi Lu
BACKGROUND: miRNA is a microRNA that negatively regulates protein expression at post-transcriptional or translational level. It is widely involved in the pathogenesis of tumors. miR-98 belongs to the let-7 family, and its overexpression can increase the sensitivity to drugs in solid cancer cells. However, the function of miR-98 in leukemia is still unclear. In this study, the effect of miR-98 on drug resistance and proliferation of leukemia cells were investigated. METHODS: Real-time quantitative polymerase chain reaction analyzed the expression difference between miR-98 and E2F1 in leukemia cell lines, K562 and K562/A02...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28716136/up-regulation-of-cdk16-by-multiple-mechanisms-in-hepatocellular-carcinoma-promotes-tumor-progression
#16
Yitao Wang, Xian Qin, Tao Guo, Pengpeng Liu, Ping Wu, Zhisu Liu
BACKGROUND: Hepatocellular carcinoma (HCC) remains difficult to cure due to lack of effective treatment and the molecular mechanisms are complex and not completely understood. In this study, We investigated the role of CDK16 in tumor progression of HCC. METHODS: We interrogated the expression level of CDK16 by polymerase chain reaction and immunohistochemistry(IHC) and studied its clinical significance. The functional role of CDK16 on HCC was studied via gain and loss of function in vitro and in vivo...
July 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28716024/mir-661-promotes-tumor-invasion-and-metastasis-by-directly-inhibiting-rb1-in-non-small-cell-lung-cancer
#17
Feiye Liu, Yanjun Cai, Xiaoxiang Rong, Jinzhang Chen, Dayong Zheng, Lu Chen, Junyi Zhang, Rongcheng Luo, Peng Zhao, Jian Ruan
BACKGROUND: Aberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation. METHODS: Expression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models...
July 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28711427/temporal-remodeling-of-the-cell-cycle-accompanies-differentiation-in-the-drosophila-germline
#18
Taylor D Hinnant, Arturo A Alvarez, Elizabeth T Ables
Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell...
September 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28710039/cloning-expression-pattern-and-potential-role-of-apoptosis-inhibitor-5-in-the-termination-of-embryonic-diapause-and-early-embryo-development-of-artemia-sinica
#19
Shuang Zhang, Feng Yao, Ting Jing, Mengchen Zhang, Wei Zhao, Xiangyang Zou, Linlin Sui, Lin Hou
During the embryonic development of Artemia sinica, the diapause phenomenon can be induced by high salinity or low temperature conditions. The diapause embryo at the gastrula stage is maintained under the threat of apoptosis to guarantee the embryo's normal development. In this process, apoptosis inhibitor proteins play vital roles in protecting embryos against apoptosis. Apoptosis inhibitor5 (API5) plays a pivotal role in regulating the cell cycle and preventing programmed cell death after growth factor starvation...
July 11, 2017: Gene
https://www.readbyqxmd.com/read/28704519/e2f1-somatic-mutation-within-mirna-target-site-impairs-gene-regulation-in-colorectal-cancer
#20
Camila M Lopes-Ramos, Bruna P Barros, Fernanda C Koyama, Paola A Carpinetti, Julia Pezuk, Nayara T S Doimo, Angelita Habr-Gama, Rodrigo O Perez, Raphael B Parmigiani
BACKGROUND: Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. METHODS: We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation...
2017: PloS One
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