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Transcriptional regulation

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https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#1
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#2
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28538660/regulatory-plasticity-of-earthworm-wmt-2-gene-expression
#3
Victoria Drechsel, Karl Schauer, Maja Šrut, Martina Höckner
Metallothioneins (MTs) are multifunctional proteins occurring throughout the animal kingdom. While the expression and transcriptional regulation of MTs is well-studied in vertebrates, the mechanism of MT activation is still unknown for most invertebrates. Therefore, we examined wMT-2 gene regulation and expression patterns in Lumbricus rubellus and L. terrestris. Transcription levels, the occupation of DNA binding sites, the expression of putative transcriptional regulators, and promotor DNA methylation were determined...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538214/profiling-and-bioinformatic-analysis-of-circular-rna-expression-regulated-by-c-myc
#4
Qiheng Gou, Ke Wu, Jian-Kang Zhou, Yuxin Xie, Lunxu Liu, Yong Peng
The c-Myc transcription factor is involved in cell proliferation, cell cycle and apoptosis by activating or repressing transcription of multiple genes. Circular RNAs (circRNAs) are widely expressed non-coding RNAs participating in the regulation of gene expression. Using a high-throughput microarray assay, we showed that Myc regulates the expression of certain circRNAs. A total of 309 up- and 252 down-regulated circRNAs were identified. Among them, randomly selected 8 circRNAs were confirmed by real-time PCR...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28538211/the-oxido-metabolic-driver-atf4-enhances-temozolamide-chemo-resistance-in-human-gliomas
#5
Daishi Chen, Manfred Rauh, Michael Buchfelder, Ilker Y Eyupoglu, Nicolai Savaskan
Malignant gliomas are devastating neoplasia with limited curative treatment options. Temozolomide (TMZ, Temcat®, Temodal® or Temodar®) is a first-line treatment for malignant gliomas but the development of drug resistance remains a major concern. Activating transcription factor 4 (ATF4) is a critical oxido-metabolic regulator in gliomas, and its role in the pathogenesis of TMZ-resistance remains elusive. We investigated the effect of TMZ on human glioma cells under conditions of enhanced ATF4 expression (ATF4OE) and ATF4 knock down (ATF4KD)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28538187/bivariate-genomic-footprinting-detects-changes-in-transcription-factor-activity
#6
Songjoon Baek, Ido Goldstein, Gordon L Hager
In response to activating signals, transcription factors (TFs) bind DNA and regulate gene expression. TF binding can be measured by protection of the bound sequence from DNase digestion (i.e., footprint). Here, we report that 80% of TF binding motifs do not show a measurable footprint, partly because of a variable cleavage pattern within the motif sequence. To more faithfully portray the effect of TFs on chromatin, we developed an algorithm that captures two TF-dependent effects on chromatin accessibility: footprinting and motif-flanking accessibility...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538183/runx1-eto-and-runx1-evi1-differentially-reprogram-the-chromatin-landscape-in-t-8-21-and-t-3-21-aml
#7
Justin Loke, Salam A Assi, Maria Rosaria Imperato, Anetta Ptasinska, Pierre Cauchy, Yura Grabovska, Natalia Martinez Soria, Manoj Raghavan, H Ruud Delwel, Peter N Cockerill, Olaf Heidenreich, Constanze Bonifer
Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538180/regnase-1-maintains-iron-homeostasis-via-the-degradation-of-transferrin-receptor-1-and-prolyl-hydroxylase-domain-containing-protein-3-mrnas
#8
Masanori Yoshinaga, Yoshinari Nakatsuka, Alexis Vandenbon, Daisuke Ori, Takuya Uehata, Tohru Tsujimura, Yutaka Suzuki, Takashi Mino, Osamu Takeuchi
Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1(-/-) mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538179/hand2-target-gene-regulatory-networks-control-atrioventricular-canal-and-cardiac-valve-development
#9
Frédéric Laurent, Ausra Girdziusaite, Julie Gamart, Iros Barozzi, Marco Osterwalder, Jennifer A Akiyama, Joy Lincoln, Javier Lopez-Rios, Axel Visel, Aimée Zuniga, Rolf Zeller
The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#10
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537926/vitamin-d3-induces-vitamin-d-receptor-and-hdac11-binding-to-relieve-the-promoter-of-the-tight-junction-proteins
#11
Feng-Hua Liu, Shan-Shan Li, Xiao-Xi Li, Shuai Wang, Mao-Gang Li, Li Guan, Tian-Gang Luan, Zhi-Gang Liu, Zhan-Ju Liu, Ping-Chang Yang
Intestinal epithelial barrier dysfunction and vitamin D (VitD)-deficiency play a critical role in a large number of diseases. The histone deacetylases (HDAC) are associated with a large number of immune diseases. This study tests a hypothesis that the interaction between VitD and HDAC is associated with the regulation of epithelial barrier functions. In this study, human intestinal epithelial cell line, T84 cells, was cultured into monolayers to be used as a model to test the epithelial barrier functions. We observed that in a VitD-deficient environment, the T84 monolayer barrier function was compromised...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537912/braf-mek-inhibitors-promote-cd47-expression-that-is-reversible-by-erk-inhibition-in-melanoma
#12
Fen Liu, Chen Chen Jiang, Xu Guang Yan, Hsin-Yi Tseng, Chun Yan Wang, Yuan Yuan Zhang, Hamed Yari, Ting La, Margaret Farrelly, Su Tang Guo, Rick F Thorne, Lei Jin, Qi Wang, Xu Dong Zhang
The expression of CD47 on the cancer cell surface transmits "don't eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses. Here we report that oncogenic activation of ERK plays an important role in transcriptional activation of CD47 through nuclear respiratory factor 1 (NRF-1) in melanoma cells. Treatment with BRAF/MEK inhibitors upregulated CD47 in cultured melanoma cells and fresh melanoma isolates. Similarly, melanoma cells selected for resistance to the BRAF inhibitor vemurafenib expressed higher levels of CD47...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537876/activation-of-perk-branch-of-er-stress-mediates-homocysteine-induced-bkca%C3%A2-channel-dysfunction-in-coronary-artery-via-foxo3a-dependent-regulation-of-atrogin-1
#13
Wen-Tao Sun, Xiang-Chong Wang, Shiu-Kwong Mak, Guo-Wei He, Xiao-Cheng Liu, Malcolm John Underwood, Qin Yang
The molecular mechanism of endoplasmic reticulum (ER) stress in vascular pathophysiology remains inadequately understood. We studied the role of ER stress in homocysteine-induced impairment of coronary dilator function, with uncovering the molecular basis of the effect of ER stress on smooth muscle large-conductance Ca2+-activated K+ (BKCa) channels. The vasodilatory function of BKCa channels was studied in a myograph using endothelium-denuded porcine small coronary arteries. Primary cultured porcine coronary artery smooth muscle cells were used for mRNA and protein measurements and current recording of BKCa channels...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537875/n-myc-downstream-regulated-gene-1-promotes-oxaliplatin-triggered-apoptosis-in-colorectal-cancer-cells-via-enhancing-the-ubiquitination-of-bcl-2
#14
Xiao Yang, Fan Zhu, Chaoran Yu, Jiaoyang Lu, Luyang Zhang, Yanfeng Lv, Jing Sun, Minhua Zheng
N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535628/-expression-and-clinical-significance-of-long-non-coding-rna-ccat1-in-gastric-cancer
#15
T Shan, Y G Chen, B Hong, H Zhou, J Z Xia
Objective: To investigate the expression and clinical significance of long non-coding RNA colon cancer associated transcript-1 (CCAT1) in gastric cancer (GC), and to further explore the effect of CCAT1 on cell proliferation of GC. Methods: The mRNA expressions of CCAT1 in GC tissues and matched adjacent normal tissues from 62 patients who received resection for gastric carcinoma between January 2013 and May 2015 in Nanjing Medical University Affiliated Wuxi Second Hospital and expressions in GC cell lines were assessed by quantitative real-time PCR (qRT-PCR)...
May 16, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535533/malat1-modulates-tgf-%C3%AE-1-induced-endothelial-to-mesenchymal-transition-through-downregulation-of-mir-145
#16
Yin Xiang, Yachen Zhang, Yong Tang, Qianhui Li
BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535417/ezrin-nf-kb-activation-regulates-epithelial-mesenchymal-transition-induced-by-egf-and-promotes-metastasis-of-colorectal-cancer
#17
Yingru Li, Zhaoyu Lin, Bin Chen, Shuang Chen, Zhipeng Jiang, Taicheng Zhou, Zehui Hou, Youyuan Wang
There is growing evidence that epithelial mesenchymal-transition (EMT) plays significant roles in terms of tumor metastasis. There are a lot of cytokines inducing EMT of tumor cells, EGF is one of the important cytokines.Ezrin is a connexin between the cytoskeleton and the cell membrane, which is closely related to the morphological movement and metastasis of tumor cells.EGF can activate Ezrin and affects cell motility. In recent years, many studies have shown that NF-kB acts as an important transcription factor, involving in the process of EMT...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28535415/dual-hypopigmentary-effects-of-punicalagin-via-the-erk-and-akt-pathways
#18
Jun Seob Shin, Jun Hee Cho, Hana Lee, Hyo-Soon Jeong, Myo-Kyoung Kim, Hye-Young Yun, Nyoun Soo Kwon, Dong-Seok Kim
Punicalagin is a phenolic compound with antioxidant properties. However, the effects of punicalagin on melanin synthesis have been poorly evaluated. Therefore, we investigated the effects of punicalagin on melanogenesis in Mel-Ab cells. Punicalagin significantly inhibited melanin synthesis in a dose-dependent manner. In accordance with the melanin content, punicalagin also dose-dependently decreased tyrosinase activity. Punicalagin did not directly inhibit tyrosinase in a cell-free system but did downregulate the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28535373/a-molecular-switch-regulating-cell-fate-choice-between-muscle-progenitor-cells-and-brown-adipocytes
#19
Yitai An, Gang Wang, Yarui Diao, Yanyang Long, Xinrong Fu, Mingxi Weng, Liang Zhou, Kun Sun, Tom H Cheung, Nancy Y Ip, Hao Sun, Huating Wang, Zhenguo Wu
During mouse embryo development, both muscle progenitor cells (MPCs) and brown adipocytes (BAs) are known to derive from the same Pax7(+)/Myf5(+) progenitor cells. However, the underlying mechanisms for the cell fate control remain unclear. In Pax7-null MPCs from young mice, several BA-specific genes, including Prdm16 and Ucp1 and many other adipocyte-related genes, were upregulated with a concomitant reduction of Myod and Myf5, two muscle lineage-determining genes. This suggests a cell fate switch from MPC to BA...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535261/recruitment-of-a-lineage-specific-virulence-regulatory-pathway-promotes-intracellular-infection-by-a-plant-pathogen-experimentally-evolved-into-a-legume-symbiont
#20
Delphine Capela, Marta Marchetti, Camille Clérissi, Anthony Perrier, Dorian Guetta, Carine Gris, Marc Valls, Alain Jauneau, Stéphane Cruveiller, Eduardo P C Rocha, Catherine Masson-Boivin
Ecological transitions between different lifestyles, such as pathogenicity, mutualism and saprophytism, have been very frequent in the course of microbial evolution, and often driven by horizontal gene transfer. Yet, how genomes achieve the ecological transition initiated by the transfer of complex biological traits remains poorly known. Here we used experimental evolution, genomics, transcriptomics and high-resolution phenotyping to analyze the evolution of the plant pathogen Ralstonia solanacearum into legume symbionts, following the transfer of a natural plasmid encoding the essential mutualistic genes...
May 23, 2017: Molecular Biology and Evolution
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