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https://www.readbyqxmd.com/read/27913635/screening-and-analysis-of-janelia-flylight-project-enhancer-gal4-strains-identifies-multiple-gene-enhancers-active-during-hematopoiesis-in-normal-and-wasp-challenged-drosophila-larvae
#1
Tsuyoshi Tokusumi, Yumiko Tokusumi, Mark S Brahier, Victoria Lam, Jessica R Stoller-Conrad, Paul T Kroeger, Robert A Schulz
A GFP expression screen has been conducted on greater than one thousand Janelia FlyLight Project enhancer-Gal4 lines to identify transcriptional enhancers active in the larval hematopoietic system. A total of 190 enhancers associated with 87 distinct genes showed activity in cells of the third instar larval lymph gland and hemolymph. That is, gene enhancers were active in cells of the lymph gland posterior signaling center (PSC), medullary zone (MZ), and/or cortical zone (CZ), while certain of the transcriptional control regions were active in circulating hemocytes...
December 2, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27906700/update-on-lipid-species-and-paediatric-nonalcoholic-fatty-liver-disease
#2
Jake P Mann, Ariel E Feldstein, Valerio Nobili
PURPOSE OF REVIEW: To describe the recent advances in our understanding of fatty acids and lipids in paediatric nonalcoholic fatty liver disease (NAFLD) and their future implications. RECENT FINDINGS: Data have been accumulated to suggest that ceramides are the main drivers of hepatic insulin resistance in NAFLD, and inhibition of ceramide synthesis improves histology in mice.Saturated fatty acids formed by de novo lipogenesis generate increased lipotoxicity compared with dietary-derived saturated fatty acids...
November 30, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27903963/cdh1-regulates-e2f1-degradation-in-response-to-differentiation-signals-in-keratinocytes
#3
Randeep K Singh, Lina Dagnino
The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902457/tfdp3-confers-chemoresistance-in-minimal-residual-disease-within-childhood-t-cell-acute-lymphoblastic-leukemia
#4
Ming Chu, Kailin Yin, Yujun Dong, Pingzhang Wang, Yun Xue, Peng Zhou, Yuqi Wang, Yuedan Wang
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889452/an-rb-ezh2-complex-mediates-silencing-of-repetitive-dna-sequences
#5
Charles A Ishak, Aren E Marshall, Daniel T Passos, Carlee R White, Seung J Kim, Matthew J Cecchini, Sara Ferwati, William A MacDonald, Christopher J Howlett, Ian D Welch, Seth M Rubin, Mellissa R W Mann, Frederick A Dick
Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments...
November 12, 2016: Molecular Cell
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
#6
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...
November 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27880827/correction-e2f1-and-tfdp1-regulate-pitx1-expression-in-normal-and-osteoarthritic-articular-chondrocytes
#7
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0165951.].
2016: PloS One
https://www.readbyqxmd.com/read/27871936/commd9-promotes-tfdp1-e2f1-transcriptional-activity-via-interaction-with-tfdp1-in-non-small-cell-lung-cancer
#8
Weihua Zhan, Wenjuan Wang, Tianyu Han, Caifeng Xie, Tingting Zhang, Mingxi Gan, Jian-Bin Wang
COMMD protein family is an evolutionarily conserved gene family implicated in a number of critical processes including inflammation, copper homeostasis, sodium balance, endosomal sorting and cancer. In an effort to profile the expression pattern of COMMD family in several non-small cell lung cancer (NSCLC) cell lines, we found that compared with that in human bronchial epithelial (HBE) cells, the mRNA expression levels of five COMMD genes including COMMD3, COMMD4, COMMD5, COMMD6 and COMMD8 were significantly down-regulated, whereas COMMD9 was up-regulated in NSCLC cell lines...
November 19, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27871087/the-hdm2-mdm2-inhibitor-nvp-cgm097-inhibits-tumor-cell-proliferation-and-shows-additive-effects-with-5-fluorouracil-on-the-p53-p21-rb-e2f1-cascade-in-the-p53wildtype-neuroendocrine-tumor-cell-line-got1
#9
Clemens Reuther, Vera Heinzle, Svenja Nölting, Sabine Herterich, Stefanie Hahner, Ensar Halilovic, Sébastien Jeay, Jens U Wuerthner, Elke Tatjana Aristizabal Prada, Gerald Spöttl, Julian Maurer, Christoph J Auernhammer
No abstract text is available yet for this article.
November 21, 2016: Neuroendocrinology
https://www.readbyqxmd.com/read/27835866/ppar%C3%AE-a-predictor-of-patient-survival-in-glioma-inhibits-cell-growth-through-the-e2f1-mir-19a-feedback-loop
#10
Yan Shi, Tao Tao, Ning Liu, WenKang Luan, Jin Qian, Rui Li, Qi Hu, Yan Wei, Junxia Zhang, Yongping You
Nuclear receptors such as peroxisome proliferator-activated receptor α (PPARα) are potential therapeutic targets. In this study, we found that PPARα expression was lower in high grade gliomas and PPARα was an independent prognostic factor in GBM patients. PPARα agonism or overexpression inhibited glioma cell proliferation, invasion, and aerobic glycolysis as well as suppressed glioma growth in an orthotopic model. Bioinformatic analysis and luciferase reporter assays showed that miR-19a decreased PPARα expression...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835575/helicobacter-pylori-infection-related-long-noncoding-rna-lncrna-af147447-inhibits-gastric-cancer-proliferation-and-invasion-by-targeting-muc2-and-up-regulating-mir-34c
#11
Xiaoying Zhou, Han Chen, Li Zhu, Bo Hao, Weifeng Zhang, Jie Hua, Huiyuan Gu, Wujuan Jin, Guoxin Zhang
Long non-coding RNAs (lncRNAs) were shown to play critical roles in cancer biology. We investigated whether H. pylori infection could promote gastric cancer by regulating lncRNAs expression. Differentially expressed lncRNAs between H. pylori positive and negative tissues were identified by microarray and validated by qRT-PCR. Our results indicated that H. pylori positive tissues have a specific profile of lncRNAs. Cell biological assays with siRNA-mediated knockdown or lentivirus vector-mediated over-expression were performed to probe the functional relevance of the lncRNAs...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825926/the-interaction-mode-of-the-acidic-region-of-the-cell-cycle-transcription-factor-dp1-with-tfiih
#12
Masahiko Okuda, Keigo Araki, Kiyoshi Ohtani, Yoshifumi Nishimura
The heterodimeric transcription factor E2F1-DP1 plays crucial roles in coordinating gene expression during G1/S cell cycle progression. For transcriptional activation, the transactivation domain (TAD) of E2F1 is known to interact with the TATA-binding protein of TFIID and the p62 subunit of TFIIH. It is generally believed that DP1 facilitates E2F1 binding to target DNA and does not possess a TAD. Here, we show that an acidic region of DP1, whose function has remained elusive, binds to the plekstrin homology (PH) domain of p62 with higher affinity than that of E2F1 and contributes to transcriptional activation...
November 4, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27821436/histone-h3-lysine-4-trimethylation-h3k4me3-lysine-27-trimethylation-h3k27me3-and-lysine-27-acetylation-h3k27ac-contribute-to-the-transcriptional-repression-of-solute-carrier-family-47-member-2-in-renal-cell-carcinoma
#13
Qinqin Yu, Yanqing Liu, Xiaoli Zheng, Qianying Zhu, Zhuowei Shen, Hua Wang, Huadong He, Nengming Lin, Huidi Jiang, Lushan Yu, Su Zeng
In recent years, finding effective biomarkers for identifying early stage cancer and predicating prognosis is crucial for renal cell carcinoma (RCC) diagnosis and treatment. In this study, a dramatic decrease of the solute carrier family 47 member 2 (SLC47A2) mRNA in RCC comparing with the paired adjacent non-tumor tissues from patients at low TNM stage was observed. Thus, patients with SLC47A2 transcriptional repression are susceptible to RCC. Little is known about the regulation mechanism of SLC47A2. We found that it was a bivalent gene which was enriched with both histone H3 lysine 4 trimethylation (H3K4me3) and lysine 27 trimethylation (H3K27me3)...
November 7, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27818180/rac1-mediated-dna-damage-and-inflammation-promote-nf2-tumorigenesis-but-also-limit-cell-cycle-progression
#14
Yuhao Shi, Saumya R Bollam, Shannon M White, Sean Z Laughlin, Garrett T Graham, Mandheer Wadhwa, Hengye Chen, Chan Nguyen, Jeremie Vitte, Marco Giovannini, Jeffery Toretsky, Chunling Yi
Merlin encoded by the Nf2 gene is a bona fide tumor suppressor that has been implicated in regulation of both the Hippo-Yap and Rac1-Pak1 pathways. Using genetically engineered murine liver models, we show that co-deletion of Rac1 with Nf2 blocks tumor initiation but paradoxically exacerbates hepatomegaly induced by Nf2 loss, which can be suppressed either by treatment with pro-oxidants or by co-deletion of Yap. Our results suggest that while Yap acts as the central driver of proliferation during Nf2 tumorigenesis, Rac1 primarily functions as an inflammation switch by inducing reactive oxygen species that, on one hand, induce nuclear factor κB signaling and expression of inflammatory cytokines, and on the other activate p53 checkpoint and senescence programs dampening the cyclin D1-pRb-E2F1 pathway...
November 21, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27802335/e2f1-and-tfdp1-regulate-pitx1-expression-in-normal-and-osteoarthritic-articular-chondrocytes
#15
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/27793841/phospholipase-d1-acts-through-akt-topb1-and-rb1-to-regulate-the-e2f1-dependent-apoptotic-program-in-cancer-cells
#16
Dong Woo Kang, Shin Wha Lee, Won Chan Hwang, Bo Hui Lee, Yong-Seok Choi, Young-Ah Suh, Kang-Yell Choi, Do Sik Min
The RB1/E2F1 signaling pathway is frequently deregulated in colorectal cancer and has been suggested to intersect with Wnt/β-catenin and PI3K/Akt pathways, but molecular evidence for this link is lacking. In this study, we demonstrate that Phospholipase D1 (PLD1), a transcriptional target of β-catenin/TCF4, orchestrates functional interactions between these pathways during intestinal tumor development. Overexpression of PLD1 in intestinal epithelial cells protected cells from apoptosis induced by PLD1 ablation in the Apcmin/+ mouse model of intestinal tumorigenesis...
October 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27789274/h19-noncoding-rna-an-independent-prognostic-factor-regulates-essential-rb-e2f-and-cdk8-%C3%AE-catenin-signaling-in-colorectal-cancer
#17
Masahisa Ohtsuka, Hui Ling, Cristina Ivan, Martin Pichler, Daisuke Matsushita, Matthew Goblirsch, Verena Stiegelbauer, Kunitoshi Shigeyasu, Xinna Zhang, Meng Chen, Fnu Vidhu, Geoffrey A Bartholomeusz, Yuji Toiyama, Masato Kusunoki, Yuichiro Doki, Masaki Mori, Shumei Song, Jillian R Gunther, Sunil Krishnan, Ondrej Slaby, Ajay Goel, Jaffer A Ajani, Milan Radovich, George A Calin
The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function...
October 19, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27780824/klf6-suppresses-metastasis-of-clear-cell-renal-cell-carcinoma-via-transcriptional-repression-of-e2f1
#18
Xu Zhang, Yu Gao, Hongzhao Li, Xin Ma, Yang Fan, Dong Ni, Yu Zhang, Qingbo Huang, Kan Liu, Xin-Tao Li, Lei Wang, Liang-You Gu, Yuanxin Yao, Qing Ai, Qingshan Du, Erlin Song
The transcription factor KLF6 has an essential role in the development and metastasis of multiple human cancers. Paradoxically, KLF6 expression was found to be attenuated in primary metastatic clear cell renal cell carcinoma (ccRCC), such that it is unclear how KLF6 affects malignant progression in this setting. In this study, we demonstrate that KLF6 attenuation in renal cells is sufficient to promote E2F1-mediated epithelial-mesenchymal transition and metastatic prowess. In a mouse xenograft model of human ccRCC, silencing KLF6 increased tumor cell proliferation and malignant character, whereas E2F1 silencing reversed these properties...
October 25, 2016: Cancer Research
https://www.readbyqxmd.com/read/27779207/hbv-core-promoter-mutations-and-akt-upregulate-s-phase-kinase-associated-protein-2-to-promote-postoperative-hepatocellular-carcinoma-progression
#19
Lubiao Chen, Lin Gu, Yurong Gu, Hongbo Wang, Meihai Deng, Zania Stamataki, Ye Htun Oo, Yuehua Huang
Mutations in the hepatitis B virus (HBV) core promoter (CP) have been shown to be associated with hepatocellular carcinoma (HCC). The CP region overlaps HBV X gene, which activates AKT to regulate hepatocyte survival. However, the cooperation between these two cascades in HCC progression remains poorly understood. Here, we assayed virological factors and AKT expression in liver tissues from 56 HCC patients with better prognoses (BHCC, ≥5-year survival) and 58 with poor prognoses (PHCC, <5-year survival) after partial liver resection...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#20
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
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