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https://www.readbyqxmd.com/read/28087635/rb-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#1
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
Retinoblastoma (RB) is a tumor suppressor gene which regulates cell cycle entry to S phase via E2F transcription factors. Using knockout (KO) mice, it has been described that Rb plays a role in cell migration and differentiation in developing and adult brain as well as apoptosis. In addition, the RB family is required for the self-renewal and survival of human embryonic stem cells (ESCs). However, little is known about the role of this gene in human brain development. Here, we investigated the role of RB in cerebral organoids from human ESCs deficient for RB...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28077784/identification-and-characterization-of-hpv-independent-cervical-cancers
#2
Carolyn E Banister, Changlong Liu, Lucia Pirisi, Kim E Creek, Phillip J Buckhaults
BACKGROUND: Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 and E7 is thought to be necessary to maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, and most experimental therapies specifically target E6/E7. We investigated the presence and expression of HPV in cervical cancer, to correlate HPV oncogene expression with clinical and molecular features of these tumors that may be relevant to new targeted therapies...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076433/enhanced-rb-e2f-and-tsc-mtor-pathways-induce-synergistic-inhibition-in-pdgf-induced-proliferation-in-vascular-smooth-muscle-cells
#3
Yue Li, Xuan Li, Jie Liu, Wei Guo, Hongchao Zhang, Jianchang Wang
Platelet-derived growth factor (PDGF) plays an essential role in proliferation of vascular smooth muscle cells (VSMCs). The Rb/E2F and TSC/mTOR pathways contribute to the proliferation of VSMCs, but its exact roles in PDGF-induced proliferation are unclear. In this study, we demonstrated the roles of Rb/E2F and TSC/mTOR pathways in PDGF-induced proliferation in VSMCs. We found that PDGF stimulates the activity of E2F and mTOR pathways, and knockdown of either Rb or TSC2 increases PDGF-induced proliferation in VSMCs...
2017: PloS One
https://www.readbyqxmd.com/read/28042030/ectopic-expression-of-the-cdk-inhibitor-p21-cip1-enhances-deregulated-e2f-activity-and-increases-cancer-cell-specific-cytotoxic-gene-expression-mediated-by-the-arf-tumor-suppressor-promoter
#4
Kenta Kurayoshi, Ayumi Shiromoto, Eiko Ozono, Ritsuko Iwanaga, Andrew P Bradford, Keigo Araki, Kiyoshi Ohtani
In cancer treatment, specifically targeting cancer cells is important for optimal therapeutic efficacy. One strategy is to utilize a cancer specific promoter to express a cytotoxic gene or a viral gene required for replication. In this approach, the therapeutic window is dependent on the relative promoter activity in cancer cells versus normal cells. Therefore, a promoter with optimal cancer cell-specificity should be used. The tumor suppressor ARF promoter, which specifically responds to deregulated E2F activity, is a potent candidate...
December 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27983535/e2f-transcription-factors-associated-with-up-regulated-genes-in-glioblastoma
#5
Flávia S Donaires, Paulo R D V Godoy, Giovana S Leandro, Elza T Sakamoto-Hojo
BACKGROUND: Glioblastoma corresponds to the most common and malignant brain tumor in adults. Patients have a median survival of approximately one year from diagnosis due to poor response to therapy. OBJECTIVE: We applied bioinformatics approaches to predict transcription factors (TF) that are deregulated in glioblastoma in an attempt to point out molecular targets for therapy. METHODS: Up-regulated genes in glioblastoma selected from public microarray data were submitted to two TF association analyses...
December 9, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27940962/rb-localizes-to-dna-double-strand-breaks-and-promotes-dna-end-resection-and-homologous-recombination-through-the-recruitment-of-brg1
#6
Renier Vélez-Cruz, Swarnalatha Manickavinayaham, Anup K Biswas, Regina Weaks Clary, Tolkappiyan Premkumar, Francesca Cole, David G Johnson
The retinoblastoma (RB) tumor suppressor is recognized as a master regulator that controls entry into the S phase of the cell cycle. Its loss leads to uncontrolled cell proliferation and is a hallmark of cancer. RB works by binding to members of the E2F family of transcription factors and recruiting chromatin modifiers to the promoters of E2F target genes. Here we show that RB also localizes to DNA double-strand breaks (DSBs) dependent on E2F1 and ATM kinase activity and promotes DSB repair through homologous recombination (HR), and its loss results in genome instability...
November 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27929073/rna-sequencing-of-chorionic-villi-from-recurrent-pregnancy-loss-patients-reveals-impaired-function-of-basic-nuclear-and-cellular-machinery
#7
Siim Sõber, Kristiina Rull, Mario Reiman, Piret Ilisson, Pirkko Mattila, Maris Laan
Recurrent pregnancy loss (RPL) concerns ~3% of couples aiming at childbirth. In the current study, transcriptomes and miRNomes of 1(st) trimester placental chorionic villi were analysed for 2 RPL cases (≥6 miscarriages) and normal, but electively terminated pregnancies (ETP; n = 8). Sequencing was performed on Illumina HiSeq 2000 platform. Differential expression analyses detected 51 (27%) transcripts with increased and 138 (73%) with decreased expression in RPL compared to ETP (DESeq: FDR P < 0...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27923835/rb-loss-promotes-prostate-cancer-metastasis
#8
Chellappagounder Thangavel, Ettickan Boopathi, Yi Liu, Alex Haber, Adam Ertel, Anshul Bhardwaj, Sankar Addya, Noelle Williams, Steve Ciment, Paolo Cotzia, Jeffry L Dean, Adam E Snook, Chris McNair, Matthew A Price, James R Hernandez, Shuang G Zhao, Ruth Birbe, James B McCarthy, Eva A Turely, Kenneth J Pienta, Felix Y Feng, Adam P Dicker, Karen E Knudsen, Robert B Den
RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a pro-metastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelia-mesenchyme translation, motility and invasion by cancer cells. Genetic modulation or pharmacological inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27922680/identification-of-key-genes-induced-by-platelet-rich-plasma-in-human-dermal-papilla-cells-using-bioinformatics-methods
#9
Haiyan Shen, Hanxiao Cheng, Haihua Chen, Jufang Zhang
Dermal papilla cells (DPCs) are located at the base of hair follicles, and are known to induce hair follicle regeneration. Platelet-rich plasma (PRP) functions in hair follicle regeneration. To investigate the influence of PRP on DPCs, the present study analyzed RNA‑seq data of human hair dermal papilla cells (HHDPCs) that were treated or untreated by PRP. The data included in the RNA‑seq were from two normal and two treated HHDPC samples. Following identification by Cuffdiff software, differentially expressed genes (DEGs) underwent enrichment analyses, and protein-protein interaction networks were constructed using Cytoscape software...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27919948/long-noncoding-rna-snar-regulates-proliferation-migration-and-invasion-of-triple-negative-breast-cancer-cells
#10
Jeeyeon Lee, Jin Hyang Jung, Yee Soo Chae, Ho Yong Park, Wan Wook Kim, Soo Jung Lee, Jae-Hwan Jeong, Seung Hee Kang
AIM: We evaluated the role of long noncoding ribonucleic acid (lncRNA) in breast cancer cell lines by quantitative reverse transcription-polymerase change reaction. MATERIALS AND METHODS: The effects of small NF90-associated RNA (snaR) with RNA interference on proliferation, migration and invasion of MDA-MB-231 cells were observed by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, wound healing and transwell assay. RESULTS: Among 90 lncRNAs, E2F transcription factor 4, p107/p130-binding (E2F4) antisense, insulin-like growth factor 2 antisense (IGF2AS), snaR, and small nucleolar RNA host gene 5 (SNHG5) were up-regulated in MDA-MB-231 and 7SK, antisense noncoding RNA in the INK4 locus (ANRIL), IGF2AS, Nespas, p53 mRNA, and snaR were up-regulated in MCF-7 cells...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27892792/e2fl1-is-a-meiosis-specific-transcription-factor-in-the-protist-tetrahymena-thermophila
#11
Jing Zhang, Miao Tian, Guan-Xiong Yan, Anura Shodhan, Wei Miao
Members of the E2F family of transcription factors have been reported to regulate the expression of genes involved in cell cycle control, DNA replication, and DNA repair in multicellular eukaryotes. Here, E2FL1, a meiosis-specific E2F transcription factor gene, was identified in the model ciliate Tetrahymena thermophila. Loss of this gene resulted in meiotic arrest prior to anaphase I. The cytological experiments revealed that the meiotic homologous pairing was not affected in the absence of E2FL1, but the paired homologous chromosomes did not separate and assumed a peculiar tandem arrangement...
November 28, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27888801/common-profiles-of-notch-signaling-differentiate-disease-free-survival-in-luminal-type-a-and-triple-negative-breast-cancer
#12
Magdalena Orzechowska, Dorota Jędroszka, Andrzej K Bednarek
Breast cancer (BC) is characterized by high heterogeneity regarding its biology and clinical characteristics. The Notch pathway regulates such processes as organ modeling and epithelial-to-mesenchymal transition (EMT).The aim of the study was to determine the effect of differential expression of Notch members on disease-free survival (DFS) in luminal type A (lumA) and triple negative (TN) BC.The differential expression of 19 Notch members was examined in a TCGA BC cohort. DFS analysis was performed using the log-rank test (p<0...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888102/the-phosphatidyl-inositol-3-kinase-pathway-does-not-suppress-activation-of-the-arf-and-bim-genes-by-deregulated-e2f1-activity
#13
Kenta Kurayoshi, Junko Okuno, Eiko Ozono, Ritsuko Iwanaga, Andrew P Bradford, Kazuyuki Kugawa, Keigo Araki, Kiyoshi Ohtani
The transcription factor E2F plays crucial roles in tumor suppression by activating pro-apoptotic genes such as the tumor suppressor ARF. The regulation of the ARF gene is distinct from that of growth-related E2F targets, in that it is specifically activated by deregulated E2F activity, induced by over-expression of E2F or forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. The phosphatidyl inositol 3 kinase (PI3K) pathway was reported to suppress expression of some atypical pro-apoptotic genes by over-expressed E2F1...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27864908/e2f-transcription-factor-2-variants-as-predictive-biomarkers-for-recurrence-risk-in-patients-with-squamous-cell-carcinoma-of-the-oropharynx
#14
Yuncheng Li, Erich M Sturgis, Lijun Zhu, Xiaoli Cao, Qingyi Wei, Hua Zhang, Guojun Li
Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P < 0...
November 19, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27858503/high-throughput-sequencing-of-two-populations-of-extracellular-vesicles-provides-an-mrna-signature-that-can-be-detected-in-the-circulation-of-breast-cancer-patients
#15
Andrew Conley, Valentina R Minciacchi, Dhong Hyun Lee, Beatrice S Knudsen, Beth Y Karlan, Luigi Citrigno, Giuseppe Viglietto, Muneesh Tewari, Michael R Freeman, Francesca Demichelis, Dolores Di Vizio
Extracellular vesicles (EVs) contain a wide range of RNA types with a reported prevalence of non-coding RNA. To date a comprehensive characterization of the protein coding transcripts in EVs is still lacking. We performed RNA-Sequencing (RNA-Seq) of two EV populations and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions. However, these two EV populations exhibited a common mRNA signature that, in comparison to their donor cells, was significantly enriched in mRNAs encoding E2F transcriptional targets and histone proteins...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27821477/interchangeable-roles-for-e2f-transcriptional-repression-by-the-retinoblastoma-protein-and-p27kip1-cdk-regulation-in-cell-cycle-control-and-tumor-suppression
#16
Michael J Thwaites, Matthew J Cecchini, Daniel T Passos, Ian Welch, Frederick A Dick
The mammalian G1-S phase transition is controlled by the opposing forces of cyclin dependent kinases (CDK) and the retinoblastoma protein (pRB). Here we present evidence for systems level control of cell cycle arrest by pRB-E2F and p27-CDK regulation. By introducing a point mutant allele of pRB that is defective for E2F repression (Rb1(G)) into a p27(KIP1) null background (Cdkn1b(-/-)), both E2F transcriptional repression and CDK regulation are compromised. These double mutant Rb1(G/G); Cdkn1b(-/-) mice are viable and phenocopy Rb1(+/-) mice in developing pituitary adenocarcinomas, even though neither single mutant strain is cancer prone...
November 7, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27819669/a-cdk2-activity-signature-predicts-outcome-in-cdk2-low-cancers
#17
S R McCurdy, M Pacal, M Ahmad, R Bremner
The role of cyclin-dependent kinase 2 (CDK2) in cancer is controversial. A major hurdle is the availability of tools to easily assess its activity across many samples. Here, we introduce a transcriptional signature to specifically track CDK2 activity. It responds to genetic and chemical perturbations in the CDK-RB-E2F axis, correlates with mitotic rate in vitro and in vivo and reacts rapidly to changes in CDK2 activity during cell cycle progression. We find that CDK2 activity is specifically elevated in human testes, mirroring its critical function in mice, and report very distinct profiles across human cancers...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27816815/dreams-make-plant-cells-to-cycle-or-to-become-quiescent
#18
REVIEW
Zoltán Magyar, László Bögre, Masaki Ito
Cell cycle phase specific oscillation of gene transcription has long been recognized as an underlying principle for ordered processes during cell proliferation. The G1/S-specific and G2/M-specific cohorts of genes in plants are regulated by the E2F and the MYB3R transcription factors. Mutant analysis suggests that activator E2F functions might not be fully required for cell cycle entry. In contrast, the two activator-type MYB3Rs are part of positive feedback loops to drive the burst of mitotic gene expression, which is necessary at least to accomplish cytokinesis...
December 2016: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/27802335/e2f1-and-tfdp1-regulate-pitx1-expression-in-normal-and-osteoarthritic-articular-chondrocytes
#19
Martin Pellicelli, Cynthia Picard, DaShen Wang, Patrick Lavigne, Alain Moreau
We previously reported a loss-of-PITX1 expression in patients suffering of knee/hip osteoarthritis (OA). Search for the mechanism underlying this event led us to discover that PITX1 repression was triggered by the aberrant nuclear accumulation of Prohibitin (PHB1), an E2F1 co-repressor, in OA articular chondrocytes. In the current study, we assessed in details the involvement of E2F transcription factors in regulating PITX1 expression. We also analyzed other genes that are similarly regulated by E2F in regard to osteoarthritis...
2016: PloS One
https://www.readbyqxmd.com/read/27801668/upregulation-of-mir-99a-is-associated-with-poor-prognosis-of-acute-myeloid-leukemia-and-promotes-myeloid-leukemia-cell-expansion
#20
Xiaohui Si, Xiaoyun Zhang, Xing Hao, Yunan Li, Zizhen Chen, Yahui Ding, Hui Shi, Jie Bai, Yingdai Gao, Tao Cheng, Feng-Chun Yang, Yuan Zhou
Leukemia stem cells (LSCs) can resist available treatments that results in disease progression and/or relapse. To dissect the microRNA (miRNA) expression signature of relapse in acute myeloid leukemia (AML), miRNA array analysis was performed using enriched LSCs from paired bone marrow samples of an AML patient at different disease stages. We identified that miR-99a was significantly upregulated in the LSCs obtained at relapse compared to the LSCs collected at the time of initial diagnosis. We also found that miR-99a was upregulated in LSCs compared to non-LSCs in a larger cohort of AML patients, and higher expression levels of miR-99a were significantly correlated with worse overall survival and event-free survival in these AML patients...
October 27, 2016: Oncotarget
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