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https://www.readbyqxmd.com/read/29115924/transcription-factor-e2f1-promotes-emt-by-regulating-zeb2-in-small-cell-lung-cancer
#1
Tingting Wang, Xufang Chen, Weiwei Qiao, Lijun Kong, Daqing Sun, Zunling Li
BACKGROUND: Epithelial-mesenchymal transition (EMT) is an early event in tumour invasion and metastasis, and widespread and distant metastasis at early stages is the typical biological behaviour in small cell lung cancer (SCLC). Our previous reports showed that high expression of the transcription factor E2F1 was involved in the invasion and metastasis of SCLC, but the role of E2F1 in the process of EMT in SCLC is unknown. METHODS: Immunohistochemistry was performed to evaluate the expressions of EMT related markers...
November 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29115436/sirt5-promotes-cell-proliferation-and-invasion-in-hepatocellular-carcinoma-by-targeting-e2f1
#2
Liang Chang, Liang Xi, Yubin Liu, Rui Liu, Zhongshi Wu, Zhixiang Jian
Sirtuin 5 (SIRT5) is a member of the NAD+‑dependent class III protein deacetylases. Although it is known that SIRT5 deacetylates and activates urate oxidase in the liver mitochondria of mice, the mechanism of SIRT5 in the proliferation of hepatocellular carcinoma (HCC) remains to be fully elucidated. The present study investigated the expression and functional significance of SIRT5 in HCC, and examined the relevant mechanism. SIRT5 was found to be upregulated in HCC tissues and cell lines, and the higher expression of SIRT5 indicated poorer overall survival...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115381/proliferation-of-vascular-smooth-muscle-cells-under-inflammation-is-regulated-by-nf-%C3%AE%C2%BAb-p65-microrna-17-rb-pathway-activation
#3
Dong Yang, Chen Sun, Jing Zhang, Shu Lin, Lin Zhao, Lun Wang, Ruoran Lin, Junyuan Lv, Shijie Xin
Inflammation and excessive proliferation of vascular smooth muscle cells (VSMCs) have key roles in various vascular disorders, including restenosis, atherosclerosis and pulmonary artery hypertension. However, the underlying mechanism remains unclear. The present study investigated the role of nuclear factor-κB (NF-κB) and microRNA (miRNA) in the regulation of VSMC proliferation under inflammatory conditions. It was demonstrated that miR‑17 stimulated the proliferation of VSMCs, enhanced cell cycle G1/S transition, and increased levels of proliferating cell nuclear antigen and E2F1...
October 25, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29108454/pten-physically-interacts-with-and-regulates-e2f1-mediated-transcription-in-lung-cancer
#4
Prerna Malaney, Emily Palumbo, Jonathan Semidey-Hurtado, Jamaal Hardee, Katherine Stanford, Jaymin J Kathiriya, Deepal Patel, Zhi Tian, Diane Allen-Gipson, Vrushank Davé
PTEN phosphorylation at its C-terminal (C-tail) serine/threonine cluster negatively regulates its tumor suppressor function. However, the consequence of such inhibition and its downstream effects in driving lung cancer remain unexplored. Herein, we ascertain the molecular mechanisms by which phosphorylation compromises PTEN function, contributing to lung cancer. Replacement of the serine/threonine residues with alanine generated PTEN-4A, a phosphorylation-deficient PTEN mutant, which suppressed lung cancer cell proliferation and migration...
November 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29108247/regulator-of-g-protein-signaling-4-inhibits-human-melanoma-cells-proliferation-and-invasion-through-the-pi3k-akt-signaling-pathway
#5
Xiaotong Xue, Lihua Wang, Xianguang Meng, Jing Jiao, Ningning Dang
Melanoma is a tumor produced by skin melanocytes, which has a high metastatic rate and poor prognosis. So far, plenty of work has been done on melanoma, but mechanisms underlying melanoma development have not been fully elucidated. Here we identified regulator of G protein signaling 4(RGS4) as novel therapeutic target for malignant melanoma and its regulating effect on melanoma. We found that endogenous RGS4 expression was much lower in melanoma tissues and cells. In A375 cell line with low endogenous RGS4 expression, the function of RGS4 was detected by up-regulation its expression with pcDNA3...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100415/the-e2f-activators-control-multiple-mitotic-regulators-and-maintain-genomic-integrity-through-sgo1-and-bubr1
#6
Miyoung Lee, Yainyrette Rivera-Rivera, Carlos S Moreno, Harold I Saavedra
The E2F1, E2F2, and E2F3a transcriptional activators control proliferation. However, how the E2F activators regulate mitosis to maintain genomic integrity is unclear. Centrosome amplification (CA) and unregulated spindle assembly checkpoint (SAC) are major generators of aneuploidy and chromosome instability (CIN) in cancer. Previously, we showed that overexpression of single E2F activators induced CA and CIN in mammary epithelial cells, and here we show that combined overexpression of E2F activators did not enhance CA...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29089331/prevalence-of-aflatoxin-associated-tp53r249s-mutation-in-hepatocellular-carcinoma-in-hispanics-in-south-texas
#7
Jingjing Jiao, Weibo Niu, Ying Wang, Keith A Baggerly, Yuanqing Ye, Xifeng Wu, Dewitt Davenport, Jose Luis Almeda, Monica M Betancourt-Garcia, R Armour Forse, Heather L Stevenson, Gordon P Watt, Joseph B McCormick, Susan P Fisher-Hoch, Laura Beretta
We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas.We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and restriction fragment length polymorphism. TP53R249S mutation was detected in 3 out of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas...
October 31, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29050342/role-of-the-cyp3a4-mediated-11-12-epoxyeicosatrienoic-acid-pathway-in-the-development-of-tamoxifen-resistant-breast-cancer
#8
Nguyen Thi Thuy Phuong, Ji Won Kim, Jung-Ae Kim, Jang Su Jeon, Ji-Yoon Lee, Wen Jun Xu, Jin Won Yang, Sang Kyum Kim, Keon Wook Kang
Epoxyeicosatrienoic acid (EET) production via cytochrome P450 (CYP) epoxygenases closely correlates with the progression of breast cancer. However, its role in the development of chemoresistant breast cancers has yet to be elucidated. Here, we found that CYP3A4 expression and its epoxy-product, 11,12-epoxyeicosatrienoic acid (11,12-EET) was enhanced in tamoxifen (TAM)-resistant MCF-7 (TAMR-MCF-7) breast cancer cells compared to control MCF-7 cells. Treatment of TAMR-MCF-7 cells with ketoconazole and azamulin (selective CYP3A4 inhibitors) or 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an EET antagonist) inhibited cellular proliferation and recovered the sensitivity to 4-hydroxytamoxifen...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050152/-effect-of-transcription-factor-e2f1-expression-on-the-invasion-of-prostate-cancer
#9
X C Bi, X Y Pu, J M Liu, S Huang
Objective: To investigate the effect of transcription factor E2F1 on the invasion of prostate cancer and its clinical significance. Methods: A stable inhibition of E2F1 prostate cancer cell line PC3 was established. The E2F1 and relative invasion biomarker protein expression level of the transfected cells was detected by Western blot. The PC3 cells were divided into two groups: the control group and sh-E2F1 group, cell invasion assay and cell scratch test were used to detect the number of cell migration in the experiment time...
September 26, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29048668/celastrol-downregulates-e2f1-to-induce-growth-inhibitory-effects-in-hepatocellular-carcinoma-hepg2-cells
#10
Liang Ma, Lei Peng, Sheng Fang, Bangguo He, Zi Liu
Celastrol, a natural compound extracted from Tripterygium wilfordii, is known to exhibit potential anticancer activities in various types of tumor cells. E2F1 is reported to be overexpressed in several types of human tumors and its inactivation may be a valuable novel potential therapeutic strategy for cancer treatment. However, the molecular mechanism underlying the pro-apoptotic effects of celastrol on hepatocellular carcinoma (HCC) cells remains unclear, and E2F1-targeted compounds have been rarely identified...
September 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048367/regulation-of-e2f1-transcription-factor-by-ubiquitin-conjugation
#11
REVIEW
Laurence Dubrez
Ubiquitination is a post-translational modification that defines the cellular fate of intracellular proteins. It can modify their stability, their activity, their subcellular location, and even their interacting pattern. This modification is a reversible event whose implementation is easy and fast. It contributes to the rapid adaptation of the cells to physiological intracellular variations and to intracellular or environmental stresses. E2F1 (E2 promoter binding factor 1) transcription factor is a potent cell cycle regulator...
October 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29039472/e2f1-silencing-inhibits-migration-and-invasion-of-osteosarcoma-cells-via-regulating-ddr1-expression
#12
Zhaofeng Wang, Xianjie Sun, Yi Bao, Juanfen Mo, Hengchao Du, Jichao Hu, Xingen Zhang
In the present study, knockdown of E2F1 impaired the migration and invasion of osteosarcoma cells. Further analysis showed that E2F1 knockdown decreased the expression of discoidin domain receptor 1 (DDR1) which plays a crucial role in many fundamental processes such as cell differentiation, adhesion, migration and invasion. Luciferase and ChIP assays confirmed that E2F1 silencing attenuated the expression of DDR1 through disrupting E2F1-mediated transcription of DDR1 in osteosarcoma cells. Similarly with the effect of E2F1 silencing, DDR1 knockdown weakened the migratory and invasive capabilities of osteosarcoma cells; while overexpression of DDR1 resulted in a significant increase of cell motility and invasiveness, even after knocking down E2F1...
December 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29026085/ezh2-enables-germinal-centre-formation-through-epigenetic-silencing-of-cdkn1a-and-an-rb-e2f1-feedback-loop
#13
Wendy Béguelin, Martín A Rivas, María T Calvo Fernández, Matt Teater, Alberto Purwada, David Redmond, Hao Shen, Matt F Challman, Olivier Elemento, Ankur Singh, Ari M Melnick
The EZH2 histone methyltransferase is required for B cells to form germinal centers (GC). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21(Cip1)). Deletion of Cdkn1a rescues the GC reaction in Ezh2 (-/-) mice. Using a 3D B cell follicular organoid system that mimics the GC reaction, we show that depletion of EZH2 suppresses G1 to S phase transition of GC B cells in a Cdkn1a-dependent manner. GC B cells of Cdkn1a (-/-) Ezh2 (-/-) mice have high levels of phospho-Rb, indicating that loss of Cdkn1a enables progression of cell cycle...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28994157/genome-wide-association-study-and-annotating-candidate-gene-networks-affecting-age-at-first-calving-in-nellore-cattle
#14
R R Mota, S E F Guimarães, M R S Fortes, B Hayes, F F Silva, L L Verardo, M J Kelly, C F de Campos, J D Guimarães, R R Wenceslau, J M Penitente-Filho, J F Garcia, S Moore
We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17...
October 9, 2017: Journal of Animal Breeding and Genetics, Zeitschrift Für Tierzüchtung und Züchtungsbiologie
https://www.readbyqxmd.com/read/28992682/nanocurcumin-mediated-down-regulation-of-telomerase-via-stimulating-tgf%C3%AE-1-signaling-pathway-in-hepatocellular-carcinoma-cells
#15
Molood Shariati, Samira Hajigholami, Ziba Veisi Malekshahi, Maliheh Entezari, Narges Bodaghabadi, Majid Sadeghizadeh
Background: Curcumin, extracted from turmeric, represents enormous potential to serve as an anticancer agent. Telomerase is viewed as a prominent molecular target of curcumin, and Transforming growth factor-β1 (TGFβ1) has proven to be a major inhibitory signaling pathway for telomerase activity. In the current study, we aimed to explore suppressive effects of nanocurcumin on telomerase expression through TGFβ1 pathway in a hepatocellular carcinoma cell line (Huh7). Methods: MTT assay was used to determine the effect of nonocurcumin on viability of Huh7 cells...
October 10, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28992046/phosphorylated-e2f1-is-stabilized-by-nuclear-usp11-to-drive-peg10-gene-expression-and-activate-lung-epithelial-cells
#16
Dan Wang, Jing Zhao, Shuang Li, Jianxin Wei, Ling Nan, Rama K Mallampalli, Nathaniel M Weathington, Haichun Ma, Yutong Zhao
Phosphorylation affects ubiquitination, stability, and activity of transcriptional factors, thus regulating various cellular functions. E2F transcriptional factor 1 (E2F1) regulates paternally expressed imprinted gene 10 (Peg10) expression, thereby promoting cell proliferation. However, the effect of E2F1 stability on Peg10 expression and the molecular regulation of E2F1 stability by its phosphorylation have not been well demonstrated. Here, we describe a new pathway in which phosphorylation of E2F1 by GSK3β increases E2F1 association with the deubiquitinating enzyme, ubiquitin-specific protease 11 (USP11), which removes K63-linked ubiquitin chains thereby preventing E2F1 degradation in the nuclei...
September 14, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28991226/lsd1-promotes-s-phase-entry-and-tumorigenesis-via-chromatin-co-occupation-with-e2f1-and-selective-h3k9-demethylation
#17
Y He, Y Zhao, L Wang, L R Bohrer, Y Pan, L Wang, H Huang
Histone H3 lysine-9 (H3K9) methylation is essential for retinoblastoma protein (RB)-mediated heterochromatin formation, epigenetic silencing of S-phase genes and permanent cell cycle arrest or cellular senescence. Besides as an H3K4 demethylase, lysine-specific demethylase-1 (LSD1) has been shown to promote H3K9 demethylation. However, it is unexplored whether LSD1 has a causal role in regulating cell cycle entry and senescence. Here we demonstrate that genetic depletion or pharmacological inhibition of LSD1 triggers G1 arrest and cellular senescence...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28978043/gtse1-a-novel-tead4-e2f1-target-gene-involved-in-cell-protrusions-formation-in-triple-negative-breast-cancer-cell-models
#18
Debora Stelitano, Yamila Peche Leticia, Emiliano Dalla, Martin Monte, Silvano Piazza, Claudio Schneider
GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC). Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28972179/the-hnrnp-raly-regulates-transcription-and-cell-proliferation-by-modulating-the-expression-of-specific-factors-including-the-proliferation-marker-e2f1
#19
Nicola Cornella, Toma Tebaldi, Lisa Gasperini, Jarnail Singh, Richard A Padgett, Annalisa Rossi, Paolo Macchi
The heterogeneous nuclear ribonucleoproteins (hnRNPs) form a large family of RNA-binding proteins that exert numerous functions in RNA metabolism. RALY is a member of the hnRNP family that binds poly-U rich elements within several RNAs and regulates the expression of specific transcripts. RALY is upregulated in different types of cancer, and its downregulation impairs cell cycle progression. However, RALY's role in regulating RNA levels remains elusive. Here, we show that numerous genes coding for factors involved in transcription and cell cycle regulation exhibit an altered expression in RALY-downregulated HeLa cells, consequently causing impairments in transcription, cell proliferation and cell cycle progression...
September 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28964969/e2f6-protein-levels-modulate-drug-induced-apoptosis-in-cardiomyocytes
#20
Jennifer L Major, Maysoon Salih, Balwant S Tuana
The E2F/Rb pathway regulates cell growth, differentiation, and death. In particular, E2F1 promotes apoptosis in all cells including those of the heart. E2F6, which represses E2F activity, was found to induce dilated cardiomyopathy in the absence of apoptosis in murine post-natal heart. Here we evaluate the anti-apoptotic potential of E2F6 in neonatal cardiomyocytes (NCM) from E2F6-Tg hearts which showed significantly less caspase-3 cleavage, a lower Bax/Bcl2 ratio, and improved cell viability in response to CoCl2 exposure...
December 2017: Cellular Signalling
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