• Title/Summary/Keyword: Interference regulation

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Lentivirus-mediated shRNA Interference Targeting SLUG Inhibits Lung Cancer Growth and Metastasis

  • Wang, Yao-Peng;Wang, Ming-Zhao;Luo, Yi-Ren;Shen, Yi;Wei, Zhao-Xia
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.4947-4951
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    • 2012
  • Objective: Lung cancer is a deadly cancer, whose kills more people worldwide than any other malignancy. SLUG (SNAI2, Snail2) is involved in the epithelial mesenchymal transition in physiological and in pathological contexts and is implicated in the development and progression of lung cancer. Methods: We constructed a lentivirus vector with SLUG shRNA (LV-shSLUG). LV-shSLUG and a control lentivirus were infected into the non-small cell lung cancer cell A549 and real-time PCR, Western blot and IHC were applied to assess expression of the SLUG gene. Cell proliferation and migration were detected using MTT and clony formation methods. Results: Real-time PCR, Western Blot and IHC results confirmed down-regulation of SLUG expression by its shRNA by about 80%~90% at both the mRNA and protein levels. Knockdown of SLUG significantly suppressed lung cancer cell proliferation. Furthermore, knockdown of SLUG significantly inhibited lung cancer cell invasion and metastasis. Finally, knockdown of SLUG induced the down-regulation of Bcl-2 and up-regulation of E-cadherin. Conclusion: These results indicate that SLUG is a newly identified gene associated with lung cancer growth and metastasis. SLUG may serve as a new therapeutic target for the treatment of lung cancer in the future.

Manganese and Iron Interaction: a Mechanism of Manganese-Induced Parkinsonism

  • Zheng, Wei
    • Environmental Mutagens and Carcinogens
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    • v.23 no.4
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    • pp.115-130
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    • 2003
  • Idiopathic Parkinson's disease (IPD) represents a common neurodegenerative disorder. While epidemiological studies have suggested a number of risk factors including age, gender, race, and inherited disorder, the cumulative evidence supports the view that environmental or occupational exposure to certain chemicals may contribute to the initiation and progress of Parkinsonism. More recently, clinical and laboratory investigations have led to the theory that dysregulation of iron, an essential metal to body function, may underlie IPD by initiating free radical reaction, diminishing the mitochondrial energy production, and provoking the oxidative cytotoxicity. The participation of iron in neuronal cell death is especially intriguing in that iron acquisition and regulation in brain are highly conservative and thus vulnerable to interference from other metals that bear the similar chemical reactivity. Manganese neurotoxicity, induced possibly by altering iron homeostasis, is such an example. In fact, the current interest in manganese neurotoxicology stems from two primary concerns: its clinical symptoms that resemble Parkinson's disease and its increased use as an antiknock agent to replace lead in gasoline. This article will commence with addressing the current understanding of iron-associated neurodegenerative damage. The major focus will then be devoted to the mechanism whereby manganese alters iron homeostasis in brain.

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Huntingtin-interacting protein 1-related is required for accurate congression and segregation of chromosomes

  • Park, Sun-Joo
    • BMB Reports
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    • v.43 no.12
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    • pp.795-800
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    • 2010
  • Huntingtin-interacting protein 1-related (HIP1r) is known to function in clathrin-mediated endocytosis and regulation of the actin cytoskeleton, which occurs continuously in non-dividing cells. This study reports a new function for HIP1r in mitosis. Green fluorescent protein-fused HIP1r localizes to the mitotic spindles. Depletion of HIP1r by RNA interference induces misalignment of chromosomes and prolonged mitosis, which is associated with decreased proliferation of HIP1r-deficeint cells. Chromosome misalignment leads to missegregation and ultimately production of multinucleated cells. Depletion of HIP1r causes persistent activation of the spindle checkpoint in misaligned chromosomes. These findings suggest that HIP1r plays an important role in regulating the attachment of spindle microtubules to chromosomes during mitosis, an event that is required for accurate congression and segregation of chromosomes. This finding may provide new insights that improve the understanding of various human diseases involving HIP1r as well as its fusion genes.

A Robust Algorithm for Roughness Laser Measurement based on Light Power Regulation against Specimen Changes

  • Seo Young Ho;Ahn Jung Hwan
    • Journal of Mechanical Science and Technology
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    • v.19 no.5
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    • pp.1131-1137
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    • 2005
  • Methods for measuring surface roughness based on light reflectivity have advantages over methods based on light interference or diffraction, especially in in-situ, on-the-machine and in-process applications. However, measurement inconsistencies caused by changes in the specimen are still a drawback for field applications. In this study, we propose a new feedback-based algorithm to enhance the consistency against changes in the specimen. The algorithm is deduced from simulations based on light reflectance theory with typical modeled surfaces. The proposed method is similar to a digital controller and regulates the power of reflected light. Experiments varying heights and materials, verified the improvements in robustness of the method against measurement disturbances caused by specimen changes.

RNA Binding Protein as an Emerging Therapeutic Target for Cancer Prevention and Treatment

  • Hong, Suntaek
    • Journal of Cancer Prevention
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    • v.22 no.4
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    • pp.203-210
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    • 2017
  • After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.

Novel Single-inductor Multistring-independent Dimming LED Driver with Switched-capacitor Control Technique

  • Liang, Guozhuang;Tian, Hanlei
    • Journal of Power Electronics
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    • v.19 no.1
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    • pp.1-10
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    • 2019
  • Current imbalance is the main factor affecting the lifespan of light-emitting diode (LED) lighting systems and is generally solved by active or passive approaches. Given many new lighting applications, independent control is particularly important in achieving different levels of luminance. Existing passive and active approaches have their own limitations in current sharing and independent control, which bring new challenges to the design of LED drivers. In this work, a multichannel resonant converter based on switched-capacitor control (SCC) is proposed for solving this challenge. In the resonant network of the upper and lower half-bridges, SCC is used instead of fixed capacitance. Then, the individual current of the LED array is obtained through regulation of the effective capacitance of the SCC under a fixed switching frequency. In this manner, the complexity of the control unit of the circuit and the precision of the multichannel outputs are further improved. Finally, the superior performance of the proposed LED driver is verified by simulations and a 4-channel experimental prototype with a rated output power of 20 W.

A study on performance analysis and merging techniques of sensors in water quality measurement (수질계측센서의 성능분석 및 센서 융합기술에 관한 연구)

  • Yang Keun-Ho;Yoo Byung-Kook
    • Journal of the Institute of Convergence Signal Processing
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    • v.7 no.3
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    • pp.143-148
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    • 2006
  • There are need to manage the water quality to supply an safety to consumer through pipe and reservoir the drinking water that produced in a clean water reservoir. However, a management of water quality and monitoring in reservoir have never been performed. Recently, the government has enforced standards of water quality. However, we have a inferior technology of water quality as compared with one in USA, Japan, Germany, etc. In case of water quality inspection and analysis equipments, sensor technology is very important to improve the water quality inspection and to develop the analysis equipments. In this paper, we analyze a law and a regulation for management of drinking water quality, and propose the measurement standards of drinking water quality in pH, conductivity, residual chloride, turbidity and water temperature. Then, we analyze electrode sensors that interference within pH, conductivity, residual chloride in interference experiment.

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DNA methyltransferase 3a is Correlated with Transgene Expression in Transgenic Quails

  • Jang, Hyun-Jun;Kim, Young-Min;Rengaraj, Deivendran;Shin, Young-Soo;Han, Jae-Yong
    • Journal of Animal Science and Technology
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    • v.53 no.3
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    • pp.269-274
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    • 2011
  • DNA methyltransferases (DNMTs) are closely associated with the epigenetic change and the gene silencing through the regulation of methylation status in animal genome. But, the role of DNMTs in transgene silencing has remained unclear. So, we examined whether the knockdown of DNMT influences the reactivation of transgene expression in the transgenic quails. In this study, we investigated the expression of DNMT3a, and DNMT3b in blastoderm, quail embryonic fibroblasts (QEFs) and limited embryonic tissues such as gonad, kidney, heart and liver of E6 transgenic quails (TQ2) by RT-PCR. We further analyzed the expression of DNMT3a at different stages of whole embryos during early embryonic development by qRT-PCR. DNMT3a expression was detected in all test samples; however, it showed the highest expression in E6 whole embryo. Embryonic fibroblasts collected from TQ2 quails were treated with two DNMT3a-targeted siRNAs (siDNMT3a-51 and siDNMT3a-88) for RNA interference assay, and changes in expression were then analyzed by qRT-PCR. The siDNMT3a-51 and siDNMT3a-88 reduced 53.34% and 64.64% of DNMT3a expression in TQ2 QEFs, respectively. Subsequently the treatment of each siRNA reactivated enhanced green fluorescent protein (EGFP) expression in TQ2 (224% and 114%). Our results might provide a clue for understanding the DNA methylation mechanism responsible for transgenic animal production and stable transgene expression.

Lin28 regulates the expression of neuropeptide Y receptors and oocyte-specific homeobox genes in mouse embryonic stem cells

  • Park, Geon Tae;Seo, You-Mi;Lee, Su-Yeon;Lee, Kyung-Ah
    • Clinical and Experimental Reproductive Medicine
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    • v.39 no.2
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    • pp.87-93
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    • 2012
  • Objective: Lin28 has been known to control the proliferation and pluripotency of embryonic stem cells. The purpose of this study was to determine the downstream effectors of Lin28 in mouse embryonic stem cells (mESCs) by RNA interference and microarray analysis. Methods: The control siRNA and Lin28 siRNA (Dharmacon) were transfected into mESCs. Total RNA was prepared from each type of transfected mESC and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to confirm the downregulation of Lin28. The RNAs were labeled and hybridized with an Affymetrix Gene-Chip Mouse Genome 430 2.0 array. The data analysis was accomplished by GenPlex 3.0 software. The expression levels of selected genes were confirmed by quantitative real-time RT-PCR. Results: According to the statistical analysis of the cDNA microarray, a total of 500 genes were altered in Lin28-downregulated mESCs (up-regulated, 384; down-regulated, 116). After differentially expressed gene filtering, 31 genes were selected as candidate genes regulated by Lin28 downregulation. Among them, neuropeptide Y5 receptor and oocyte-specific homeobox 5 genes were significantly upregulated in Lin28-downregulated mESCs. We also showed that the families of neuropeptide Y receptor (Npyr) and oocyte-specific homeobox (Obox) genes were upregulated by downregulation of Lin28. Conclusion: Based on the results of this study, we suggest that Lin28 controls the characteristics of mESCs through the regulation of effectors such as the Npyr and Obox families.

Radixin Knockdown by RNA Interference Suppresses Human Glioblastoma Cell Growth in Vitro and in Vivo

  • Qin, Jun-Jie;Wang, Jun-Mei;Du, Jiang;Zeng, Chun;Han, Wu;Li, Zhi-Dong;Xie, Jian;Li, Gui-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9805-9812
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    • 2014
  • Radixin, a member of the ERM (ezrin-radixin-moesin) family, plays important roles in cell motility, invasion and tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types of epithelial and lymphoid examples. However, its function in glioblastomas remains elusive. Thus, in this study, radixin gene expression was first examined in the glioblastoma cells, then suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastoma U251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cells were implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or nonsense shRNA cells. In addition, microvessel density in the tumors was significantly reduced. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin- suppressed glioblastoma U251 cells. In contrast, MMP9 was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration and invasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.