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https://www.readbyqxmd.com/read/29399152/cited2-attenuates-macrophage-recruitment-concordant-with-the-downregulation-of-ccl20-in-breast-cancer-cells
#1
Swaathi Jayaraman, Michele Doucet, Scott L Kominsky
The transcriptional co-regulator Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain-2 (CITED2) may promote breast tumor growth; however, the mechanisms by which its effects are mediated remain to be fully elucidated. Tumor-associated macrophages serve an important function in tumor development and progression and are recruited by chemotactic factors produced by cells within the tumor microenvironment. The present study assessed the effects of CITED2 silencing on macrophage recruitment in two xenograft mouse models of human breast cancer, one in which tumor growth was sensitive to CITED2 silencing (MDA-MB-231) and one in which it was insensitive (MDA-MB-468)...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29203644/cited2-restrains-pro-inflammatory-macrophage-activation-and-response
#2
Gun-Dong Kim, Riku Das, Xiaoquan Rao, Jixin Zhong, Jeffrey A Deiuliis, Diana L Ramirez-Bergeron, Sanjay Rajagopalan, Ganapati H Mahabeleshwar
Macrophages are strategically distributed in mammalian tissues and play an essential role in priming immune response. However, macrophages need to constantly strike a balance between activation and inhibition state to avoid a futile inflammatory reaction. Herein, we identify the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) as a potent repressor of macrophage pro-inflammatory activation. Gain- and loss-of-function studies revealed that CITED2 is required for optimal peroxisome proliferator-activated receptor gamma (PPARγ) activation and attendant select anti-inflammatory gene expression in macrophages...
December 4, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29072699/cited2-affects-leukemic-cell-survival-by-interfering-with-p53-activation
#3
Katharina Mattes, Gerbrig Berger, Marjan Geugien, Edo Vellenga, Hein Schepers
CITED2 (CBP/p300-interacting-transactivator-with-an-ED-rich-tail 2) is a regulator of the acetyltransferase CBP/p300 and elevated CITED2 levels are shown in a number of acute myeloid leukemia (AML). To study the in vivo role of CITED2 in AML maintenance, AML cells were transduced with a lentiviral construct for RNAi-mediated knockdown of CITED2. Mice transplanted with CITED2-knockdown AML cells (n=4) had a significantly longer survival compared to mice transplanted with control AML cells (P<0.02). In vitro, the reduction of CITED2 resulted in increased p53-mediated apoptosis and CDKN1A expression, whereas BCL2 levels were reduced...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28744016/anti-inflammatory-and-chondroprotective-effects-of-the-s-adenosylhomocysteine-hydrolase-inhibitor-3-deazaneplanocin-a-in-human-articular-chondrocytes
#4
Juliette Aury-Landas, Céline Bazille, Lyess Allas, Sara Bouhout, Christophe Chesneau, Sylvain Leclercq, Karim Boumédiene, Catherine Baugé
3-Deazaneplanocin A (DZNep) is an inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) known to inhibit EZH2, a histone methylase upregulated during osteoarthritis. In this study, we assessed its effects in human articular chondrocytes. Anti-inflammatory effects were assessed by Nitric Oxide (NO), Prostaglandin E2 (PGE2) and Metalloprotease (MMP) release in IL-1β-stimulated chondrocytes. MAPK and NFκB activation was analyzed by western blotting. Differentially expressed genes (DEG) regulated by DZNep were identified by whole-transcriptome microarray...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687891/functional-analyses-of-a-novel-cited2-nonsynonymous-mutation-in-chinese-tibetan-patients-with-congenital-heart-disease
#5
Shiming Liu, Zhaobing Su, Sainan Tan, Bin Ni, Hong Pan, Beihong Liu, Jing Wang, Jianmin Xiao, Qiuhong Chen
CITED2 gene is an important cardiac transcription factor that plays a fundamental role in the formation and development of embryonic cardiovascular. Previous studies have showed that knock-out of CITED2 in mice might result in various cardiac malformations. However, the mechanisms of CITED2 mutation on congenital heart disease (CHD) in Chinese Tibetan population are still poorly understood. In the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated Tibetan healthy controls were screened for variants in the CITED2 gene; we subsequently identified one potential disease-causing mutation p...
August 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28684114/ectopic-expression-of-cited2-prior-to-reprogramming-promotes-and-homogenises-the-conversion-of-somatic-cells-into-induced-pluripotent-stem-cells
#6
João Charneca, Ana Catarina Matias, Ana Luisa Escapa, Catarina Fernandes, André Alves, João M A Santos, Rita Nascimento, José Bragança
Cited2 plays crucial roles in mouse embryonic stem cells self-renewal, the initiation of the somatic reprogramming process into induced pluripotent stem cells (iPSC) and the suppression of cell senescence. Here, we investigated the potential of CITED2 expression in combination with the Oct4, Sox2, Klf4 and c-Myc factors for reprogramming of primary mouse embryonic fibroblasts (MEF) at passage 2 and 4. The ectopic CITED2 expression in primary MEF prior to the onset of the reprogramming process, generated iPSC with less variability in the expression of endogenous pluripotency-related genes...
September 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28501104/knockdown-of-cbp-p300-interacting-transactivator-with-glu-asp-rich-carboxy-terminal-domain-2-inhibits-cell-division-and-increases-apoptosis-in-gastric-cancer
#7
Ze Tang, Gan He, Jie Xu, Li Zhongfu
BACKGROUND: Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a pleiotropic protein associated with numerous cell functions, including transcription and differentiation. The role of CITED2 has been investigated in a number of malignancies; however, the roles of this protein in gastric cancers remain unclear. Therefore, we determined the role of CITED2 in gastric cancers. MATERIALS AND METHODS: Gastric cancer cell lines (MKN74, MKN28, 7901, and AGS) were used to assess CITED2 transcript levels...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28436679/cited2-mutations-in-conserved-regions-contribute-to-conotruncal-heart-defects-in-chinese-children
#8
Bojian Li, Tian Pu, Yang Liu, Yuejuan Xu, Rang Xu
Conotruncal heart defects (CTDs) are severe malformations of outflow tract with heterogeneous morphology. Several missense variants of CITED2 have been identified to cause CTDs in recent researches. In this study, we screened the coding regions of CITED2 in 605 Chinese children with CTDs and found two possible pathogenic mutant sites: p.Q117L and p.T257A, both located in the conserved regions of CITED2. Then, we investigated the biological and functional alterations of them. Western blotting showed low level of protein expression of mutant Q117 and T257A compared with wild-type CITED2...
July 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28273070/hypersensitive-termination-of-the-hypoxic-response-by-a-disordered-protein-switch
#9
Rebecca B Berlow, H Jane Dyson, Peter E Wright
The cellular response to hypoxia is critical for cell survival and is fine-tuned to allow cells to recover from hypoxic stress and adapt to heterogeneous or fluctuating oxygen levels. The hypoxic response is mediated by the α-subunit of the transcription factor HIF-1 (HIF-1α), which interacts through its intrinsically disordered C-terminal transactivation domain with the TAZ1 (also known as CH1) domain of the general transcriptional coactivators CBP and p300 to control the transcription of critical adaptive genes...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28115365/activation-of-ppar%C3%AE-by-endogenous-prostaglandin-j2-mediates-the-antileukemic-effect-of-selenium-in-murine-leukemia
#10
Emily R Finch, Diwakar B Tukaramrao, Laura L Goodfield, Michael D Quickel, Robert F Paulson, K Sandeep Prabhu
Supplementation with nontoxic doses of micronutrient selenium has been shown to alleviate chronic myelogenous leukemia (CML) via the elimination of leukemia stem cells (LSCs) in mice. This treatment provides a new and novel method for eliminating the LSCs that are otherwise not targeted by existing therapies. The antileukemic effect of selenium was dependent on the production of endogenous cyclopentenone prostaglandins (CyPGs), Δ-12 prostaglandin J2 (Δ(12)-PGJ2), and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2)...
March 30, 2017: Blood
https://www.readbyqxmd.com/read/28013219/the-role-of-mir-182-5p-in-hepatocarcinogenesis-of-trichloroethylene-in-mice
#11
Yan Jiang, Jiahong Chen, Cong Yue, Hang Zhang, Jian Tong, Jianxiang Li, Tao Chen
Trichloroethylene (TCE), commonly used as an industrial solvent, is ubiquitous in our living environment. TCE exposure can induce hepatocellular carcinoma (HCC) in mice, but the underlying mechanisms remain elusive. To understand the role of miRNA in the hepatocarcinogenesis of TCE, we examined the miRNA expression profiles by microarray in the liver of B6C3F1 male mice exposed to TCE at 0 or 1000 mg/kg b.w. Nine differentially expressed miRNAs were identified, out of which miR-182-5p exhibited the highest increase in expression...
March 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28008154/down-regulation-of-cited2-attenuates-breast-tumor-growth-vessel-formation-and-tgf-%C3%AE-induced-expression-of-vegfa
#12
Swaathi Jayaraman, Michele Doucet, Scott L Kominsky
While we previously demonstrated that CITED2 expression in primary breast tumor tissues is elevated relative to normal mammary epithelium and inversely correlated with patient survival, its functional impact on primary tumor development and progression remained unknown. To address this issue, we examined the effect of CITED2 silencing on the growth of human breast cancer cell lines MDA-MB-231 and MDA-MB-468 following orthotopic administration in vivo. Here, we show that CITED2 silencing significantly attenuated MDA-MB-231 primary tumor growth concordant with reduced tumor vascularization, while MDA-MB-468 primary tumor growth and tumor vascularization remained unaffected...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27907012/the-signature-of-microrna-dysregulation-in-muscle-paralyzed-by-spinal-cord-injury-includes-downregulation-of-micrornas-that-target-myostatin-signaling
#13
Rita De Gasperi, Zachary A Graham, Lauren M Harlow, William A Bauman, Weiping Qin, Christopher P Cardozo
Spinal cord injury (SCI) results in muscle atrophy, reduced force generation and an oxidative-to-glycolytic fiber type shift. The mechanisms responsible for these alterations remain incompletely understood. To gain new insights regarding mechanisms involved in deterioration of muscle after SCI, global expression profiles of miRs in paralyzed gastrocnemius muscle were compared between sham-operated (Sham) and spinal cord-transected (SCI) rats. Ingenuity Pathways Analysis of the altered miRs identified signaling via insulin, IGF-1, integrins and TGF-β as being significantly enriched for target genes...
2016: PloS One
https://www.readbyqxmd.com/read/27889473/endothelial-cells-regulate-%C3%AE-catenin-activity-in-adrenocortical-cells-via-secretion-of-basic-fibroblast-growth-factor
#14
Carolin Schwafertz, Sven Schinner, Markus C Kühn, Matthias Haase, Amelie Asmus, Birgit Mülders-Opgenoorth, Ishrath Ansurudeen, Peter J Hornsby, Henning Morawietz, Elke Oetjen, Matthias Schott, Holger S Willenberg
Endothelial cell-derived products influence the synthesis of aldosterone and cortisol in human adrenocortical cells by modulating proteins such as steroidogenic acute-regulatory (StAR) protein, steroidogenic factor (SF)-1 and CITED2. However, the potential endothelial cell-derived factors that mediate this effect are still unknown. The current study was perfomed to look into the control of β-catenin activity by endothelial cell-derived factors and to identify a mechanism by which they affect β-catenin activity in adrenocortical NCIH295R cells...
November 23, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27879404/targeting-cited2-for-angiogenesis-in-obesity-and-insulin-resistance
#15
Guanghong Jia, James R Sowers
No abstract text is available yet for this article.
December 2016: Diabetes
https://www.readbyqxmd.com/read/27874008/the-gcn5-cited2-pka-signalling-module-controls-hepatic-glucose-metabolism-through-a-camp-induced-substrate-switch
#16
Mashito Sakai, Tomoko Tujimura-Hayakawa, Takashi Yagi, Hiroyuki Yano, Masaru Mitsushima, Hiroyuki Unoki-Kubota, Yasushi Kaburagi, Hiroshi Inoue, Yoshiaki Kido, Masato Kasuga, Michihiro Matsumoto
Hepatic gluconeogenesis during fasting results from gluconeogenic gene activation via the glucagon-cAMP-protein kinase A (PKA) pathway, a process whose dysregulation underlies fasting hyperglycemia in diabetes. Such transcriptional activation requires epigenetic changes at promoters by mechanisms that have remained unclear. Here we show that GCN5 functions both as a histone acetyltransferase (HAT) to activate fasting gluconeogenesis and as an acetyltransferase for the transcriptional co-activator PGC-1α to inhibit gluconeogenesis in the fed state...
November 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27818139/cited2-cooperates-with-isl1-and-promotes-cardiac-differentiation-of-mouse-embryonic-stem-cells
#17
Ivette Pacheco-Leyva, Ana Catarina Matias, Daniel V Oliveira, João M A Santos, Rita Nascimento, Eduarda Guerreiro, Anna C Michell, Annebel M van De Vrugt, Gisela Machado-Oliveira, Guilherme Ferreira, Ibrahim Domian, José Bragança
The transcriptional regulator CITED2 is essential for heart development. Here, we investigated the role of CITED2 in the specification of cardiac cell fate from mouse embryonic stem cells (ESC). The overexpression of CITED2 in undifferentiated ESC was sufficient to promote cardiac cell emergence upon differentiation. Conversely, the depletion of Cited2 at the onset of differentiation resulted in a decline of ESC ability to generate cardiac cells. Moreover, loss of Cited2 expression impairs the expression of early mesoderm markers and cardiogenic transcription factors (Isl1, Gata4, Tbx5)...
December 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27750106/breast-cancer-osteomimicry-and-its-role-in-bone-specific-metastasis-an%C3%A2-integrative-systematic-review-of-preclinical-evidence
#18
REVIEW
Olugbenga Awolaran, Susan A Brooks, Verna Lavender
Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016...
December 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27680315/cited2-participates-in-cardiomyocyte-apoptosis-and-maternal-diabetes-induced-congenital-heart-abnormality
#19
Dongmei Su, Jun-Xian Song, Qianqian Gao, Lina Guan, Qian Li, Cuige Shi, Xu Ma
Gestational diabetes mellitus is a risk factor for abnormal heart development, but the molecular basis remains obscure. To further analyze this, the hyperglycemia rat and cell model were established in this study. The results showed that hyperglycemic rats gained significantly less weight during gestation than controls. The number of embryos per litter was significantly reduced in diabetic mothers compared to controls. Ventricular wall thickness was often decreased in the diabetic offspring and cardiomyocyte apoptosis participated in ventricular wall thinness...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27629361/microrna-expression-profiling-and-functional-annotation-analysis-of-their-targets-modulated-by-oxidative-stress-during-embryonic-heart-development-in-diabetic-mice
#20
Daoyin Dong, Yuji Zhang, E Albert Reece, Lei Wang, Christopher R Harman, Peixin Yang
Maternal pregestational diabetes mellitus (PGDM) induces congenital heart defects (CHDs). The molecular mechanism underlying PGDM-induced CHDs is unknown. microRNAs (miRNAs), small non-coding RNAs, repress gene expression at the posttranscriptional level and play important roles in heart development. We performed a global miRNA profiling study to assist in revealing potential miRNAs modulated by PGDM and possible developmental pathways regulated by miRNAs during heart development. A total of 149 mapped miRNAs in the developing heart were significantly altered by PGDM...
October 2016: Reproductive Toxicology
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