• Title/Summary/Keyword: down-regulated

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Silencing of PDK1 Gene Expression by RNA Interference Suppresses Growth of Esophageal Cancer

  • Yu, Jing;Chen, Kui-Sheng;Li, Ya-Nan;Yang, Juan;Zhao, Lu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4147-4151
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    • 2012
  • The current study was conducted to explore the inhibitory effects of a small interfering RNA (siRNA) on 3-phosphoinositide-dependent protein kinase 1 (PDK1) expression in esophageal cancer 9706 (EC9706) cells and the influence on their biological behavior. After transfection of a synthesized PDK1 siRNA, PDK1 mRNA and protein expression and the phosphorylation level of the downstream Akt protein were assessed using RT-PCR and Western blot analysis. Proliferation, apoptosis, cell invasion and in vivo tumor formation capacity were also investigated using MTT, flow cytometry, Transwell invasion trials, and nude mouse tumor transplantion, respectively. PDK1 siRNA effectively suppressed PDK1 mRNA and protein expression, and down-regulated the phosphorylation level of the Akt protein in the EC9706 cells (P < 0.05). It also inhibited cell proliferation and invasion, and promoted apoptosis; such effects were particularly obvious at 48 h and 72 h after transfection (P < 0.05). Growth of transplanted tumors was inhibited in nude mice, with decreased PDK1 expression in tumor tissues. PDK1 may be closely correlated with proliferation, apoptosis and invasion of esophageal cancer cells and thus may serve as an effective target for gene therapy.

Down-regulated MYH11 Expression Correlates with Poor Prognosis in Stage II and III Colorectal Cancer

  • Wang, Ren-Jie;Wu, Peng;Cai, Guo-Xiang;Wang, Zhi-Min;Xu, Ye;Peng, Jun-Jie;Sheng, Wei-Qi;Lu, Hong-Fen;Cai, San-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7223-7228
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    • 2014
  • The MYH11 gene may be related to cell migration and adhesion, intracellular transport, and signal transduction. However, its relationship with prognosis is still uncertain. The aim of this study was to investigate correlations between MYH11 gene expression and prognosis in 58 patients with stage II and III colorectal cancer. Quantitative real-time polymerase chain reaction was performed in fresh CRC tissues to examine mRNA expression, and immunohistochemistry was performed with paraffin-embedded specimens for protein expression. On univariate analysis, MYH11 expression at both mRNA and protein levels, perineural invasion and lymphovascular invasion were related to disease-free survival (p<0.05; log-rank test). Cancers with lower MYH11 expression were more likely to have a poor prognosis. Otherwise, MYH11 expression was unrelated to patient clinicopathological features. On multivariate analysis, low MYH11 expression proved to be an independent adverse prognosticator (p<0.05). These findings show that MYH11 can contribute to predicting prognosis in stage II and III colorectal cancers.

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

  • Wang, Da-Wei;Wang, Zhao-Hui;Wang, Ling-Ling;Song, Yang;Zhang, Gui-Zhen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7553-7558
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    • 2014
  • The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZ and Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has been shown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports have indicated that abnormal hiwi expression is associated with poorer prognosis of multiple types of human cancers, including examples in the breast. However, little is known about details of the oncogenic role of hiwi in breast cancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantly higher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymph node metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDA-MB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role of hiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up- or down-regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting roles of hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the present study confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and provided e vidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.

Anti-inflammatory effect of Samultang in human mast cell line HMC-1

  • Choi In-Young;Kim Su-Jin;Kang Tae-Hee;Lee Byung-Hee;Lee Joon-Ho;Lee Ju-Young;Kim Hyung-Min;Hong Seung-Heon;Um Jae-Young
    • Advances in Traditional Medicine
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    • v.6 no.3
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    • pp.237-244
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    • 2006
  • Samultang has been believed for prevention and remedy various blood diseases such as menstrual irregularity, anemia, and metrorrhagia. However, the mechanism that accounts for anti-inflammatory effects of the Samultang is still not fully understood. This study was designed to evaluate whether and how the Samultang could modulate the production of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 treated-human mast cell line, HMC-1. Samultang inhibited the production of tumor necrosis factor $(TNF)-\alpha$, interleukin (IL)-6, granulocyte macrophage colony stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in HMC-1. Maximal inhibition rate of $TNF-\alpha$, IL-6, GM-CSF, and VEGF by 0.1 mg/ml Samultang was about $70.73{\pm}3.0%,\;51.49{\pm}4.14%,\;54.03{\pm}2.09%$, and $47.95{\pm}7.86%$, respectively. Samultang partially blocked PMA plus A23187-induced cyclooxygenase (COX)-2 expression. In addition, Samultang inhibited activation of nuclear factor (NF)-kB, and extracellular signal-regulated kinase (ERK) activation. These results suggest that anti-inflammatory effect of Samulatng may be mediated by the suppression of cytokine production and COX-2 activation via down-regulation of NF-kB and ERK activation.

The Polysaccharide Fraction AIP1 from Artemisia iwayomogi Suppresses Apoptotic Death of the Mouse Spleen Cells in Culture

  • Hwang, Jung-Suk;Chung, Hye-Kyung;Bae, Eun-Kyong;Lee, Ah-Young;Ji, Hee-Jung;Park, Dong-Woon;Jung, Hwa-Jin;Cho, Chung-Won;Choi, Hyun-Ju;Lee, Dong-Seok;Lee, Kang-Ro;Youn, Hyun-Joo
    • Archives of Pharmacal Research
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    • v.26 no.4
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    • pp.294-300
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    • 2003
  • A polysaccharide fraction, AIP1, purified from Artemisia iwayomogi was shown to have immunomodulating and anti-tumor activities in mice. In order to determine how the AIP1 fraction exhibits the immunomodulating activity, the effect of the fraction on the apoptosis of mouse spleen cells was investigated. Treatment of the mouse spleen cells with the AIP1 fraction resulted ,in the suppression of apoptotic death and an extension of cell survival in culture, indicating that the fraction might modulate the death of spleen cells. Treatment of the mice with the AIP1 fraction in vivo also resulted in less apoptosis of the spleen cells, which indicates the physiological relevance of the anti-apoptosis effect of the fraction in vitro. A mouse gene array was used to determine the profile of the gene expression change showing a pattern of up- and down-regulated genes by the AIP1 treatment. This study provides preliminary information regarding the immunomodulatory mechanism of the AIP1 fraction.

Role of microRNA-520h in 20(R)-ginsenoside-Rg3-mediated angiosuppression

  • Keung, Man-Hong;Chan, Lai-Sheung;Kwok, Hoi-Hin;Wong, Ricky Ngok-Shun;Yue, Patrick Ying-Kit
    • Journal of Ginseng Research
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    • v.40 no.2
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    • pp.151-159
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    • 2016
  • Background: Ginsenoside-Rg3, the pharmacologically active component of red ginseng, has been found to inhibit tumor growth, invasion, metastasis, and angiogenesis in various cancer models. Previously, we found that 20(R)-ginsenoside-Rg3 (Rg3) could inhibit angiogenesis. Since microRNAs (miRNAs) have been shown to affect many biological processes, they might play an important role in ginsenoside-mediated angiomodulation. Methods: In this study, we examined the underlying mechanisms of Rg3-induced angiosuppression through modulating the miRNA expression. In the miRNA-expression profiling analysis, six miRNAs and three miRNAs were found to be up- or down-regulated in vascular-endothelial-growth-factor-induced human-umbilical-vein endothelial cells (HUVECs) after Rg3 treatment, respectively. Results: A computational prediction suggested that mature hsa-miR-520h (miR-520h) targets ephrin receptor (Eph) B2 and EphB4, and hence, affecting angiogenesis. The up-regulation of miR-520h after Rg3 treatment was validated by quantitative real-time polymerase chain reaction, while the protein expressions of EphB2 and EphB4 were found to decrease, respectively. The mimics and inhibitors of miR- 520h were transfected into HUVECs and injected into zebra-fish embryos. The results showed that overexpression of miR-520h could significantly suppress the EphB2 and EphB4 protein expression, proliferation, and tubulogenesis of HUVECs, and the subintestinal-vessel formation of the zebra fish. Conclusion: These results might provide further information on the mechanism of Rg3-induced angiosuppression and the involvement of miRNAs in angiogenesis.

Korean Red Ginseng Saponin Fraction Downregulates Proinflammatory Mediators in LPS Stimulated RAW264.7 Cells and Protects Mice against Endotoxic Shock

  • Yayeh, Taddessee;Jung, Kun-Ho;Jeong, Hye-Yoon;Park, Ji-Hoon;Song, Yong-Bum;Kwak, Yi-Seong;Kang, Heun-Soo;Cho, Jae-Youl;Oh, Jae-Wook;Kim, Sang-Keun;Rhee, Man-Hee
    • Journal of Ginseng Research
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    • v.36 no.3
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    • pp.263-269
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    • 2012
  • Korean red ginseng has shown therapeutic effects for a number of disease conditions. However, little is known about the anti-inflammatory effect of Korean red ginseng saponin fraction (RGSF) in vitro and in vivo. Therefore, in this study, we showed that RGSF containing 20(S)-protopanaxadiol type saponins inhibited nitric oxide production and attenuated the release of tumor necrotic factor (TNF)-${\alpha}$, interleukin (IL)-6, granulocyte monocyte colony stimulating factor (GMCSF), and macrophage chemo-attractant protein-1 in lipopolysaccharide (LPS) stimulated murine macrophage RAW264.7 cells. Moreover, RGSF down-regulated the mRNA expressions of inducible nitric oxide synthase, cyclooxyginase-2, IL-$1{\beta}$, TNF-${\alpha}$, GMCSF, and IL-6. Furthermore, RGSF reduced the level of TNF-${\alpha}$ in the serum and protected mice against LPS mediated endotoxic shock. In conclusion, these results indicated that ginsenosides from RGSF and their metabolites could be potential sources of therapeutic agents against inflammation.

Dermal Bioactive Properties of the Ethanol Extract from Flowers of Lespedeza bicolor (싸리꽃 에탄올 추출물의 피부(皮膚) 생리활성(生理活性) 효과)

  • Ryu, In-Sik;Lee, Seon-Jin;Lee, Sung-Won;Mun, Yeun-Ja;Woo, Won-Hong;Kim, Yeong-Mok;Lee, Jang-Choen;Lim, Kyu-Sang
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.20 no.2 s.33
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    • pp.1-9
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    • 2007
  • Objective : In this study, the ethanol extract from flowers of Lespedeza bicolor was investigated for their dermal bioactive properties related to cosmeceuticals such as depigmentation and radical scavenging effect. Results : The ethanol extract from flowers of Lespedeza bicolor showed considerable radical scavenging activity ($SC_{50}:\;10\;{\mu}g/ml$) and inhibited the production of nitric oxide (NO) in Raw 264.7 macrophages activated with the endotoxin lipopolysaccharide (LPS). Although the proliferation of B16/F10 cells was slightly decreased by the ethanol extract from flowers of Lespedeza bicolor at the concentration of $100\;{\mu}g/ml$, it did not appear necrosis. The ethanol extract from flowers of Lespedeza bicolor down-regulated melanin formation effectively. Methods : The free radical scavenging activity of Lespedeza bicolor was assayed in cell free systems using a stable free radical, 1,l-diphenyl-2-picrylhydrazyl (DPPH). Nitrite accumulated in culture medium was measured as an indicator of NO production using a Griess reaction. Cell viability was measured by MTT assay and melanin content was assessed using the method of Hosei with some modifications. Conclusions : These results suggest that the ethanol extract from flowers of Lespedeza bicolor is a potent depigmetation agent and it may be a candidate for antioxidant and anti-inflammatory agent.

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Identification of genes related to ER stress in bZIP28 gene transgenic potato plant

  • Kim, Dool Yi;Kim, Kyung Hwa;Choi, Man Soo;Ok, Hyun Choog;Kim, Jae Hyun
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.153-153
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    • 2017
  • Potato (Solanum tubersosum L.) is susceptible to various environmental stresses such as frost, high temperature, and drought. Enhancement of potato drought tolerance can reduce yield loss under drought that has negative effect on potato tuber growth. Genetic engineering can be utilized to achieve this goal, but such approaches using endogenous potato genes have rarely been applied. Since unpredictable global weather changes cause more severe and frequent water limiting conditions, improvement of potato drought tolerance can minimize such adverse effects under drought and can impact on sustainable potato production. Genetic engineering can be utilized to improve potato drought tolerance, but such approaches using endogenous potato genes have rarely been applied. We were obtained AtbZIP28 gene transgenic potato plants. It is identified transcript levels at various stress conditions, polyethylene glycol (PEG), NaCl, abscisic ${\underline{acid}}$ (ABA). Also, For identification to regulate ER stress response genes in AtbZIP28 gene transgenic potato plant, we screened seven potato genes from RNA-seq analysis under TM treatment. Five and two genes were up- and down-regulated by TM, respectively. Their expression patterns were re-examined at stress agents known to elicit TM, DTT, DMSO and salt stress.

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Serum Cytokine Levels are related to Nesfatin-1/NUCB2 Expression in the Implantation Sites of Spontaneous Abortion Model of CBA/j×DBA/2 Mice

  • Chung, Yiwa;Kim, Heejeong;Seon, Sojeong;Yang, Hyunwon
    • Development and Reproduction
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    • v.21 no.1
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    • pp.35-46
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    • 2017
  • The process of spontaneous abortion involves a complex mechanism with various cytokines, growth factors, and hormones during the pregnancy. However, the mechanism underlying spontaneous abortion by pro- and anti-inflammatory cytokines in the serum during the pregnancy is not fully understood. Therefore, the purpose of this study was to examine the relationship between the serum levels of pro- and anti-inflammatory cytokines and spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Serum levels of pro-inflammatory cytokines, such as $IFN-{\gamma}$, $IL-1{\alpha}$ and $TNF-{\alpha}$ were not increased in abortion model mice, but anti-inflammatory cytokines, such as IL-4, IL-13 and IL-1ra were decreased compared to normal pregnant mice. In addition, serum levels of chemokine, such as SDF-1, G-CSF, M-CSF, IL-16, KC and MCP-1 were decreased in abortion model mice compared to normal pregnant mice. However, the expression levels of nesfatin-1/NUCB2 mRNA and protein in the uteri of implantation sites were significantly higher in abortion model mice than normal pregnant mice. These results suggest that uterine nesfatin-1/NUCB2 expression may be down-regulated by inflammatory cytokines and chemokines in the serum of pregnant mice. Moreover, this study suggests the possibility that nesfatin-1/NUCB2 expressed in the implantation sites may be associated with the maintenance of pregnancy.