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Yali Wang, Shourong Wu, Can Huang, Yanjun Li, Hezhao Zhao, Vivi Kasim
Cancer cells typically shift their metabolism to aerobic glycolysis to fulfil the demand of energy and macromolecules in order to support their proliferation. Glucose transporter (GLUT) family-mediated glucose transport is the pacesetter of aerobic glycolysis, and thus is critical for tumor cell metabolism. Yin Yang 1 (YY1) is an oncogene crucial for tumorigenesis; however, its role in tumor cell glucose metabolism remains unclear. Here we revealed that YY1 activates GLUT3 transcription by direct binding to its promoter, and concomitantly, enhances tumor cells aerobic glycolysis...
June 5, 2018: Cancer Science
Susan I Daraiseh, Ari Kassardjian, Karen E Alexander, Raed Rizkallah, Myra M Hurt
Yin Yang 1 (YY1) is a multifunctional transcription factor that can activate or repress transcription depending on the promotor and/or the co-factors recruited. YY1 is phosphorylated in various signaling pathways and is critical for different biological functions including embryogenesis, apoptosis, proliferation, cell-cycle regulation and tumorigenesis. Here we report that YY1 is a substrate for c-Abl kinase phosphorylation at conserved residue Y254 in the spacer region. Pharmacological inhibition of c-Abl kinase by imatinib, nilotinib and GZD824, knock-down of c-Abl using siRNA, and the use of c-Abl kinase-dead drastically reduces tyrosine phosphorylation of YY1...
May 25, 2018: Biochimica et Biophysica Acta
Xin-Chun Zhang, Hong-Feng Liang, Xiao-Dong Luo, Hua-Jun Wang, Ai-Ping Gu, Chun-Ye Zheng, Qiao-Zhen Su, Jun Cai
Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia, the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB)...
May 25, 2018: Biochemical and Biophysical Research Communications
Rita Haldar, Lee Shaashua, Hagar Lavon, Yasmin A Lyons, Oded Zmora, Eran Sharon, Yehudit Birnbaum, Tanir Allweis, Anil K Sood, Iris Barshack, Steve Cole, Shamgar Ben-Eliyahu
Catecholamines and prostaglandins are secreted abundantly during the perioperative period in response to stress and surgery, and were shown by translational studies to promote tumor metastasis. Here, in a phase-II biomarker clinical trial in breast cancer patients (n=38), we tested the combined perioperative use of the β-blocker, propranolol, and the COX2-inhibitor, etodolac, scheduled for 11 consecutive perioperative days, starting 5 days before surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2&T3), and after treatment cessation (T4)...
May 22, 2018: Brain, Behavior, and Immunity
Zachery R Belak, Nicholas Ovsenek, Christopher H Eskiw
Yin-Yang 1 (YY1) is a highly conserved transcription factor possessing RNA-binding activity. A putative YY1 homologue was previously identified in the developmental model organism Strongylocentrotus purpuratus (the purple sea urchin) by genomic sequencing. We identified a high degree of sequence similarity with YY1 homologues of vertebrate origin which shared 100% protein sequence identity over the DNA- and RNA-binding zinc-finger region with high similarity in the N-terminal transcriptional activation domain...
May 23, 2018: Scientific Reports
Xiang Yin, Shuyu Wang, Yan Qi, Xudong Wang, Hongquan Jiang, Tianhang Wang, Yueqing Yang, Ying Wang, Chunting Zhang, Honglin Feng
AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A -positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling...
May 16, 2018: Molecular and Cellular Neurosciences
Botros B Shenoda, Yuzhen Tian, Guillermo M Alexander, Enrique Aradillas-Lopez, Robert J Schwartzman, Seena K Ajit
Background: Evidence is overwhelming for sex differences in pain, with women representing the majority of the chronic pain patient population. There is a need to explore novel avenues to elucidate this sex bias in the development of chronic inflammatory pain conditions. Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder, and the incidence of CRPS is greater in women than in men by ~4:1. Since neurogenic inflammation is a key feature of CRPS, dysregulation of inflammatory responses can be a factor in predisposing women to chronic pain...
2018: Journal of Pain Research
Tomoko Takimoto-Shimomura, Hisao Nagoshi, Saori Maegawa, Yuto Fujibayashi, Taku Tsukamoto, Yayoi Matsumura-Kimoto, Yoshimi Mizuno, Yoshiaki Chinen, Shinsuke Mizutani, Yuji Shimura, Shigeo Horiike, Masafumi Taniwaki, Tsutomu Kobayashi, Junya Kuroda
BACKGROUND/AIM: Bendamustine hydrochloride (BH) is a key therapeutic agent for mantle cell lymphoma (MCL), while the mechanism underlying BH-resistance has not been verified. MATERIALS AND METHODS: We compared molecular/biological characteristics of a newly-generated MCL-derived cell line KPUM-YY1 and its BH-resistant subline KPUM-YY1R. RESULTS: The growth-inhibitory IC50 for BH was 20 μM in KPUM-YY1 cells, while cell proliferation was not inhibited by up to 60 μM BH in KPUM-YY1R cells...
May 2018: Cancer Genomics & Proteomics
Angel-Carlos Román, Julián Vicente-Page, Alfonso Pérez-Escudero, Jose M Carvajal-González, Pedro M Fernández-Salguero, Gonzalo G de Polavieja
BACKGROUND: Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We use the zebrafish (Danio rerio) as a model to test the influence of histone modifications on behavior. RESULTS: We find that laboratory and isogenic zebrafish larvae show consistent individual behaviors when swimming freely in identical wells or in reaction to stimuli. This behavioral inter-individual variability is reduced when we impair the histone deacetylation pathway...
April 25, 2018: Genome Biology
Chi-Yu Lai, Chiu-Ya Lin, Chia-Chun Hsu, Kun-Yun Yeh, Guor Mour Her
Nonalcoholic fatty liver disease (NAFLD) has been associated with the function and changes in expression levels of microRNAs (miRs). MiR-7 has been proven to play an important role in many cellular processes; however, its functions in the context of liver lipogenesis remain unknown. We applied the microRNA-sponge (miR-SP) technology and generated transgenic miR-7a-SP models (hC7aSP and bC7aSP), which disrupted the activities of hepatic miR-7a and induced the early onset of NAFLD and nonalcoholic steatohepatitis (NASH) in zebrafish...
August 2018: Biochimica et Biophysica Acta
Björn Tampe, Désirée Tampe, Gunsmaa Nyamsuren, Friederike Klöpper, Gregor Rapp, Anne Kauffels, Thomas Lorf, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Samy Hakroush, Michael Zeisberg
Progression of chronic kidney disease associated with progressive fibrosis and impaired tubular epithelial regeneration is still an unmet biomedical challenge because, once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. Prompted by various studies across multiple organs demonstrating that preconditioning regimens to induce endogenous regenerative mechanisms protect various organs from later incurring acute injuries, we here aimed to gain insights into the molecular mechanisms underlying successful protection and to explore whether such pathways could be utilized to inhibit progression of chronic organ injury...
June 11, 2018: Journal of Clinical Investigation
Solenne Dumont, Soazig Le Pennec, Audrey Donnart, Raluca Teusan, Marja Steenman, Catherine Chevalier, Rémi Houlgatte, Frédérique Savagner
The PGC-1 (Peroxisome proliferator-activated receptor Gamma Coactivator-1) family of coactivators (PGC-1α, PGC-1β, and PRC) plays a central role in the transcriptional control of mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) processes. These coactivators integrate mitochondrial energy production into cell metabolism using complementary pathways. The XTC.UC1 cell line is a mitochondria-rich model of thyroid tumors whose biogenesis is almost exclusively dependent on PRC. Here we aim to propose an integrative view of the cellular pathways regulated by PRC through integration of cDNA and miRNA microarray data and chromatin immunoprecipitation results obtained from XTC...
March 23, 2018: Oncotarget
Ji-Hua Ren, Jie-Li Hu, Sheng-Tao Cheng, Hai-Bo Yu, Vincent Kam Wai Wong, Betty Yuen Kwan Law, Yong-Feng Yang, Ying Huang, Yi Liu, Wei-Xian Chen, Xue-Fei Cai, Hua Tang, Yuan Hu, Wen-Lu Zhang, Xiang Liu, Quan-Xin Long, Li Zhou, Na-Na Tao, Hong-Zhong Zhou, Qiu-Xia Yang, Fang Ren, Lin He, Rui Gong, Ai-Long Huang, Juan Chen
Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA) which serves as a template for HBV RNA transcription is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified SIRT3 as a host factor restricting HBV transcription and replication by screening seven members of Sirtuin family which is the class III histone deacetylase...
April 6, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yu Zhang, Shujin He, Renmei Mei, Yurong Kang, Jing Duan, Ran Wei, Chuqi Xiang, Yemeng Wu, Xiangtong Lu, Zhenyu Cai, Lixia Xiong
IL‑13 is a proinflammatory cytokine associated with multiple pathological conditions and the promotion of metastasis in lung cancer. Previous studies have demonstrated that IL‑13 and YY1 are associated with PI3K/AKT signaling. In addition, miR‑29a has been found to play a critical role in cell invasion in lung cancer. However, the molecular mechanism of miR‑29a underlying its involvement in IL‑13‑induced lung cancer cell invasion remains largely unknown. In the present study, we aimed to investigate the role of miR‑29a in cell invasion mediated by IL‑13 in lung cancer...
June 2018: Oncology Reports
Gabriela Antonio-Andrés, Jesus Rangel-Santiago, Belen Tirado-Rodríguez, Gustavo U Martinez-Ruiz, Miguel Klunder-Klunder, Mario I Vega, Briceida Lopez-Martinez, Elva Jiménez-Hernández, Jose Torres Nava, Aurora Medina-Sanson, Sara Huerta-Yepez
Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (MDR1/ABCB1) gene encodes P-glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of MDR1 and its relation to ALL outcomes. Analysis of the MDR1 promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of MDR1 expression and function...
April 4, 2018: Leukemia & Lymphoma
Ting-Hsuan Wu, Lingfang Shi, Jessika Adrian, Minyi Shi, Ramesh V Nair, Michael P Snyder, Peter N Kao
NF90 and splice variant NF110 are DNA- and RNA-binding proteins encoded by the Interleukin enhancer-binding factor 3 (ILF3) gene that have been established to regulate RNA splicing, stabilization and export. The roles of NF90 and NF110 in regulating transcription as chromatin-interacting proteins have not been comprehensively characterized. Here, chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) identified 9,081 genomic sites specifically occupied by NF90/NF110 in K562 cells. One third of NF90/NF110 peaks occurred at promoters of annotated genes...
2018: PloS One
Xiang Qiu, Gita Kumari, Tatiana Gerasimova, Hansen Du, Lawal Labaran, Amit Singh, Supriyo De, William H Wood, Kevin G Becker, Weiqiang Zhou, Hongkai Ji, Ranjan Sen
Immunoglobulin heavy-chain (IgH) genes are assembled by DNA rearrangements that juxtapose a variable (VH ), a diversity (DH ), and a joining (JH ) gene segment. Here, we report that in the absence of intergenic control region 1 (IGCR1), the intronic enhancer (Eμ) associates with the next available CTCF binding site located close to VH 81X via putative heterotypic interactions involving YY1 and CTCF. The alternate Eμ/VH 81X loop leads to formation of a distorted recombination center and altered DH rearrangements and disrupts chromosome conformation that favors distal VH recombination...
April 5, 2018: Molecular Cell
Tracy A Bedrosian, Carolina Quayle, Nicole Novaresi, Fred H Gage
The brain is a genomic mosaic owing to somatic mutations that arise throughout development. Mobile genetic elements, including retrotransposons, are one source of somatic mosaicism in the brain. Retrotransposition may represent a form of plasticity in response to experience. Here, we use droplet digital polymerase chain reaction to show that natural variations in maternal care mediate the mobilization of long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons in the hippocampus of the mouse brain...
March 23, 2018: Science
Jéssica Arribas Arranz, Dalia Nilufar Winter, Hans Günter Drexler, Sonja Eberth
Background: Yin Yang 1 (YY1) is a transcription factor that plays an important role during all stages of B cell differentiation. Several studies reported upregulation of YY1 in B cell derived lymphoma, indicating that it might act as an oncogene. Furthermore, aberrant YY1 expression has been associated with survival in some entities of B cell non-Hodgkin lymphoma (B-NHL), suggesting that YY1 could be a valuable biomarker in B-NHL. However, studies are controversial and methodologically disparate, partially because some studies are based on transcript levels while others rely on YY1 protein data...
2018: Biomarker Research
Kaixuan Zeng, Xiaoxiang Chen, Mu Xu, Xiangxiang Liu, Xiuxiu Hu, Tao Xu, Huiling Sun, Yuqin Pan, Bangshun He, Shukui Wang
Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] = 2...
March 16, 2018: Cell Death & Disease
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