• Title/Summary/Keyword: Down-Regulation

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Association of miR-193b Down-regulation and miR-196a up-Regulation with Clinicopathological Features and Prognosis in Gastric Cancer

  • Mu, Yong-Ping;Tang, Song;Sun, Wen-Jie;Gao, Wei-Min;Wang, Mao;Su, Xiu-Lan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8893-8900
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    • 2014
  • Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRTPCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR-196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.

Inhibition of the Interleukin-11-STAT3 Axis Attenuates Hypoxia-Induced Migration and Invasion in MDA-MB-231 Breast Cancer Cells

  • Lim, Ji-Hong
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.5
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    • pp.391-396
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    • 2014
  • Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

Performance tests result and consideration for AUTS(Advanced Urban Transit System) (차세대전동차 완성차시험 결과 및 고찰)

  • Hong, Jai-Sung;Kim, Gil-Dong;Lee, Chang-Mu;Won, Jong-Un;Lee, An-Ho;Sung, Chang-Won
    • Proceedings of the KSR Conference
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    • 2011.05a
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    • pp.1092-1096
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    • 2011
  • The "standard regulation" of the vehicles from "urban transit law" are being adopted to electric multiple unit in domestic. In the standard regulation, there are two types for EMU. One is heavy EMU for Seoul. The other is large EMU for Pusan, Daegu, Gwangju, Daejeon, Incheon. Korea Railroad Research Institute, with the assistance of the Ministry of Land, Transport and Maritime Affairs, "advanced EMU development project" are progressed, and 6th year started at September, one unit to six cars is completed. Now "urban transit vehicle performance tests are on the current progress. The main characteristics of AUTS(Advanced Urban Transit System) are as follows. One inverter control one motor, DDM(Dircet Drive Motor), no driving gear, plug door and steps, mounting and maintenance costs down, passenger convenience improvement. This paper describes the key features the next generation EMU, and performance test results, and the commercial success method of national R&D business.

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Response and transcriptional regulation of rice SUMOylation system during development and stress conditions

  • Chaikam, Vijay;Karlson, Dale T.
    • BMB Reports
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    • v.43 no.2
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    • pp.103-109
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    • 2010
  • Modification of proteins by the reversible covalent addition of the small ubiquitin like modifier (SUMO) protein has important consequences affecting target protein stability, sub-cellular localization, and protein-protein interactions. SUMOylation involves a cascade of enzymatic reactions, which resembles the process of ubiquitination. In this study, we characterized the SUMOylation system from an important crop plant, rice, and show that it responds to cold, salt and ABA stress conditions on a protein level via the accumulation of SUMOylated proteins. We also characterized the transcriptional regulation of individual SUMOylation cascade components during stress and development. During stress conditions, majority of the SUMO cascade components are transcriptionally down regulated. SUMO conjugate proteins and SUMO cascade component transcripts accumulated differentially in various tissues during plant development with highest levels in reproductive tissues. Taken together, these data suggest a role for SUMOylation in rice development and stress responses.

Control Strategy of Ratio Changing System for a Metal V-Belt CVT Adopting Primary Pressure Regulation (압력제어 방식 금속 벨트 CVT 변속비 제어 전략)

  • 최득환;김현수
    • Transactions of the Korean Society of Automotive Engineers
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    • v.10 no.3
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    • pp.201-208
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    • 2002
  • In this paper, the control strategy of ratio changing system for a metal belt CVT adopting primary pressure regulation is developed, and the shirting performance of pressure regulating type CVT with the suggested control strategy is investigated. The control strategy suggested in this study is composed of 2 feedback loop, one is speed ratio feedback and the other is primary pressure feedback. The pressure feedback is adopted to ensure prohibiting a belt slip during transient period in a fast downshift mode. Simulation results show that the system with suggested control strategy gives appropriate response time and tracking Performance for upshift and also gives a proper primary pressure which can prohibit the belt slip. In addition, it is fecund that the given system has an acceptable servo property in tracking the target speed ratio and robustness for the disturbance of line pressure.

HDAC3 acts as a negative regulator of angiogenesis

  • Park, Deokbum;Park, Hyunmi;Kim, Youngmi;Kim, Hyuna;Jeoung, Dooil
    • BMB Reports
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    • v.47 no.4
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    • pp.227-232
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    • 2014
  • Histone deacetylase-3 (HDAC3) is involved in cellular proliferation, apoptosis and transcriptional repression. However, the role of HDAC3 in angiogenesis remains unknown. HDAC3 negatively regulated the expression of angiogenic factors, such as VEGF and plasminogen activator inhibitor-1 (PAI-1). HDAC3 showed binding to promoter sequences of PAI-1. HDAC3 activity was necessary for the expression regulation of PAI-1 by HDAC3. VEGF decreased the expression of HDAC3, and the down-regulation of HDAC3 enhanced endothelial cell tube formation. HDAC3 negatively regulated tumor-induced angiogenic potential. We show the novel role of HDAC3 as a negative regulator of angiogenesis.

Positive and negative regulation of the Drosophila immune response

  • Aggarwal, Kamna;Silverman, Neal
    • BMB Reports
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    • v.41 no.4
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    • pp.267-277
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    • 2008
  • Insects mount a robust innate immune response against a wide array of microbial pathogens. The hallmark of the Drosophila humoral immune response is the rapid production of anti-microbial peptides in the fat body and their release into the circulation. Two recognition and signaling cascades regulate expression of these antimicrobial peptide genes. The Toll pathway is activated by fungal and many Gram-positive bacterial infections, whereas the immune deficiency (IMD) pathway responds to Gram-negative bacteria. Recent work has shown that the intensity and duration of the Drosophila immune response is tightly regulated. As in mammals, hyperactivated immune responses are detrimental, and the proper down-modulation of immunity is critical for protective immunity and health. In order to keep the immune response properly modulated, the Toll and IMD pathways are controlled at multiple levels by a series of negative regulators. In this review, we focus on recent advances identifying and characterizing the negative regulators of these pathways.

Effects of Gleditsia spina (GS) water extract on Gene Expression of Human Melanoma cells, by using Microarry technique (DNA chip을 이용한 조각자 추출물의 인간유래 악성 종양에 미치는 영향)

  • Park, Yong-Ho;Kim, Jong-Han;Park, Su-Yeon;Choi, Jeong-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.21 no.1
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    • pp.55-69
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    • 2008
  • Objective : This study was designed to investigated effects of Gleditsia spina (GS) on human derived melanoma cells Methods : The genetic profile for the effect of medicine on human derived melanoma cells of SK-MEL-2, was measured by using microarray technique, and the functional analysis on these genes was conducted. The network of total protein interactions was measured by using cytoscape program. Results : Total 253 genes were up-regulated and 439 genes down-regulated in cells treated with GS. Genes induced or suppressed by GS were all mainly concerned with metabolic process, regulation of biological process and protein binding. Conclusion : Suggest the possibility of GS as anti-cancer drug and cosmetic agent, and also suggest that related mechanisms are involved in regulation of intra-cellular metabolism in melanoma cells.

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Regulation of Cytokine Production by Exogenous Nitric oxide in Murine Splenocyte and Peritoneal Macrophage

  • Eun, Jae-Soon;Suh, Yong-Hoon;Kim, Dae-Keun;Jeon, Hoon
    • Archives of Pharmacal Research
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    • v.23 no.5
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    • pp.531-534
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    • 2000
  • Nitric oxide (NO), products of activated macrophages, have a great impact on the regulation of cytokine production. The role of NO in non-specific host cells is commonly accepted. On the contrary, its role as an immuno-regulatory molecule is still controversial. In this study, we have investigated the effect of NO on the production of cytokines from murine splenocytes and macrophages. S-nitroso-L-glutathione inhibited the release of both interferone-$\gamma$ and interleukin-2 produced by Th1 cells and tumor necrosis factor-$\alpha$ and interleukin-1$\beta$ produced by macrophages, but did not affect the release of interleukin-4 and interleukin-10 produced by Th2 cells. These results suggest that NO exerts a down-regulatory effect on the secretion of cytokines from Th1 cells and macrophages which are implicated in immune response. Thus, NO may have an important role as an immune-modulatory as well as effector molecule in the immune system.

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IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling

  • Lee, Won-Jun
    • IMMUNE NETWORK
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    • v.11 no.4
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    • pp.223-226
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    • 2011
  • Although exercise-induced growth factors such as Insulin-like growth factor-I (IGF-I) are known to affect various aspects of physiology in skeletal muscle cells, the molecular mechanism by which IGF-I modulates anti-inflammatory effects in these cells is presently unknown. Here, we showed that IGF-I stimulation suppresses the expression of toll-like receptor 4 (TLR4), a key innate immune receptor. A pharmacological inhibitor study further showed that PI3K/Akt signaling pathway is required for IGF-I-mediated negative regulation of TLR4 expression. Furthermore, IGF-I treatment reduced the expression of various NF-${\kappa}B$-target genes such as TNF-${\alpha}$ and IL-6. Taken together, these findings indicate that the anti-inflammatory effect of exercise may be due, at least in part, to IGF-I-induced suppression of TLR4 and subsequent downregulation of the TLR4-dependent inflammatory signaling pathway.