• Title/Summary/Keyword: Micro-Targeting

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MicroRNA-301b promotes cell proliferation and apoptosis resistance in triple-negative breast cancer by targeting CYLD

  • Song, Hongming;Li, Dengfeng;Wu, Tianqi;Xie, Dan;Hua, Kaiyao;Hu, Jiashu;Deng, Xiaochong;Ji, Changle;Deng, Yijun;Fang, Lin
    • BMB Reports
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    • v.51 no.11
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    • pp.602-607
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    • 2018
  • Aberrant expression of microRNAs (miRNAs) plays important roles in carcinogenesis and tumor progression. However, the expression and biological role of miR-301b in triple-negative breast cancer (TNBC) remains unclear. Here we aimed to evaluate the roles and mechanisms of miR-301b in TNBC cells. miR-301b expression was assessed in TNBC specimens and cell lines by quantitative Real-Time PCR (qRT-PCR). TNBC cells were transfected with miR-301b mimics, inhibitors or Cylindromatosis (CYLD) small interfering RNA (siRNA) using Lipofectamine 2000. The functional roles of miR-301b were determined by cell proliferation, colony formation, and apoptosis assays. Western blots and qRT-PCR were used to measure the expression of mRNAs and proteins in the cells. We found that miR-301b was upregulated in TNBC specimens and cell lines. Overexpression of miR-301b promoted cell proliferation in TNBC cells, while inhibited the apoptosis induced by 5-FU. CYLD was downregulated by miR-301b at both mRNA and protein levels in TNBC cells. Dual-luciferase report assay confirmed that miR-301b downregulated CYLD by direct interaction with the 3'-untranslated region(3'-UTR) of CYLD mRNA. $NF-{\kappa}B$ activation was mechanistically associated with miR-301b-mediated downregulation of CYLD. However, inhibition of miR-301b reversed all the effects of miR-301b. In conclusion, miR-301b plays an oncogenic role in TNBC possibly by downregulating CYLD and subsequently activating $NF-{\kappa}B$ p65, and this may provide a novel therapeutic approach for TNBC.

Research on Characteristics of Vegetation Subsequent to Crossing Structure of the Urban Streams - Centering on the Cases of Dorimcheon, Banghakcheon, Seongnaecheon and Yangjaecheon in Seoul - (도시하천의 횡단구조에 따른 식생분포특성 연구 -서울시 도림천, 방학천, 성내천, 양재천을 사례로-)

  • Bae, Jung-Hee;Lee, Kyong-Jae;Han, Bong-Ho
    • Korean Journal of Environment and Ecology
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    • v.22 no.3
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    • pp.268-279
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    • 2008
  • This study is aimed at typifying the crossing structure and inquiring into the characteristics of vegetation distribution by type targeting Dorimcheon(stream), Banghakcheon(stream), Seongnaecheon(stream) and some sections of Yangjaecheon(stream) in Seoul through the establishment of basic data for restoring vegetation in urban stream. This research classified the crossing structure into 56 slope types and 31 vertical types in combination with the three items, such as bank slope(vertical style, slope style) of bank, absence or presence of waterside, and revetment structure. This research derived nine slope types including SB1 (revetment of low water level-revetment with vegetation, and revetment of high water level-nature riverside) including SG5(revetment of low water-concrete, and revetment of high water level-riprap work), and three vertical types, such as VH4(bank revetment-wet masonry), and VH7(bank revetment - concrete )from the target survey areas. Among these, both revetment of low water level and high water level were found to be distributed on the longest section as the type of SG7 and VG7 structured in concrete. As a result of inquiry and analysis of micro topography structure and vegetation structure of eight major types, this research could find out the influence of crossing structure on plant vegetation according to the characteristic by typified item, but there appeared no distinct characteristic of vegetation distribution by crossing structure.

Effects of Zizyphi Spinosae Extract on Cisplatin and t-Butylhydroperoxide Induced Acute Renal Failure in Rabbits (토끼에서 cisplatin에 의해 유도된 급성 신부전시 산조인 추출물의 효과)

  • Kim, Jae Young;Kim, Chung Hui
    • Journal of Life Science
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    • v.24 no.7
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    • pp.777-783
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    • 2014
  • Cathepsin D (CtsD), an aspartyl peptidase, is involved in apoptosis, resulting in the release of cytochrome C from mitochondria in cells. Here, we investigated microRNA regulation of CtsD expression in 3T3-L1 cells. First, we observed the expression of CtsD in cells in response to doxorubicin (Dox). As expected, the level of CtsD mRNA increased in 3T3-L1 cells exposed to Dox in a dose-dependent manner. The cellular viability of ectopically expressed CtsD cells was decreased. Next, we used the miRanda program to search for particular microRNA targeting CtsD. MiR-145 was selected as a putative controller of CtsD because it had a high mirSVR score. In a reporter assay, the luciferase activity of cells containing the CtsD 3'-UTR region decreased in cells transfected with a miR-145 mimic compared to that of a control. The level of CtsD expression was down-regulated in preadipocytes ectopically expressing miR-145 and up-regulated by an miR-145 inhibitor. Cells also suppressed miR-145 expression when exposed to Dox. The miR-145 inhibitor reduced the cellular viability of 3T3-L1 cells. Taken together, these data suggest that miR-145 regulates CtsD-mediated cell death in adipocytes. These findings may have valuable implications concerning the molecular mechanism of CtsD-mediated cell death in obesity, suggesting that CtsD could be a useful therapeutic tool for the prevention and treatment of obesity by regulating fat cell numbers.

Upregulation of miR-23b Enhances the Autologous Therapeutic Potential for Degenerative Arthritis by Targeting PRKACB in Synovial Fluid-Derived Mesenchymal Stem Cells from Patients

  • Ham, Onju;Lee, Chang Youn;Song, Byeong-Wook;Lee, Se-Yeon;Kim, Ran;Park, Jun-Hee;Lee, Jiyun;Seo, Hyang-Hee;Lee, Chae Yoon;Chung, Yong-An;Maeng, Lee-So;Lee, Min Young;Kim, Jongmin;Hwang, Jihwan;Woo, Dong Kyun;Chang, Woochul
    • Molecules and Cells
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    • v.37 no.6
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    • pp.449-456
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    • 2014
  • The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23b-transfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated1 cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats

  • Hou, Qiuke;Huang, Yongquan;Zhang, Changrong;Zhu, Shuilian;Li, Peiwu;Chen, Xinlin;Hou, Zhengkun;Liu, Fengbin
    • Journal of Neurogastroenterology and Motility
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    • v.24 no.4
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    • pp.656-668
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    • 2018
  • Background/Aims MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. Methods We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. Results The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. Conclusions This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

Hydraulic Characteristics of Deep and Low Permeable Rock Masses in Gyeongju Area by High Precision Constant Pressure Injection Test (고정밀도 정압 주입시험에 의한 경주 지역 대심도 저투수성 암반 수리특성 연구)

  • Bae, SeongHo;Kim, Hagsoo;Kim, Jangsoon;Park, Eui Seob;Jo, Yeonguk;Ji, Taegu;Won, Kyung-Sik
    • Tunnel and Underground Space
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    • v.31 no.4
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    • pp.243-269
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    • 2021
  • Since the early 2010s, the social importance of research and practical projects targeting deep geological disposal of high-level nuclear waste, underground CO2 storage and characterization of deep subsurface by borehole investigation has been increasing. In this regard, there is also a significant increase in the need for in situ test technology to obtain quantitative and reliable information on the hydraulic characteristics of deep rock mass. Through years of research and development, we have independently set up Deep borehole Hydraulic Test System (DHTS) based on the key apparatuses designed and made with our own technology. Using this system, high precision constant pressure injection tests were successfully completed at the two 1 km boreholes located in Mesozoic granite and sedimentary rock regions, Gyeongju. During the field tests, it was possible to measure very low flow rate below 0.01 l/min with micro flow rate injection/control module. In this paper, the major characteristics of DHTS are introduced and also some results obtained from the high precision field tests under the deep and low permeable rock mass environment are briefly discussed.

A Study on the Differentiation of Policy Instruments According to the Characteristic Factors of Apparel Sewing Micro Manufacturers Clusters in Seoul (서울시 의류봉제 소공인클러스터의 특성요인에 따른 정책수단 차별화에 관한 연구)

  • Young-Su Jung;Joo-Sung Hwang
    • Journal of the Economic Geographical Society of Korea
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    • v.26 no.3
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    • pp.238-255
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    • 2023
  • In this study, we derived the characteristic factors of the cluster as measurable variables, and attempted to clarify the characteristics of the apparel sewing areas in Changsin-dong, Doksan-dong, and Jangwi-dong. Based on these results, a comparative analysis was conducted to see how the demand for the government's support policy differs for each agglomeration area. Materials were collected through face-to-face questionnaires targeting tenant companies in the three regions. As a result of the analysis, Changsin-dong was identified as an "innovative growth type," Doksan-dong as a "networking type," and Jangwi-dong as a "specialized localization type." As a result of the research on policy demands, the policy demands of the three agglomerations appeared different, but Changsin-dong preferred capacity building, Doksan-dong preferred information provision, and Jangwi-dong favored policy means of benefit. It was confirmed that even among clusters of the same apparel sewing industry, the formation process and characteristics are different, and as a result, the demand for policy instruments is also different. Policy recommendations include understanding the characteristics and policy demands of each agglomeration area through periodic fact-finding surveys, and recommending the establishment and implementation of differentiated support policies that match the characteristics of each agglomeration area.

Targeting of BUB1b Gene Expression in Sentinel Lymph Node Biopsies of Invasive Breast Cancer in Iranian Female Patients

  • Mansouri, Neda;Movafagh, Abolfazl;Sayad, Arezou;Pour, Atefeh Heidary;Taheri, Mohammad;Soleimani, Shahrzad;Mirzaei, Hamid Reza;Shargh, Shohreh Alizadeh;Azargashb, Eznollah;Bazmi, Haleh;Moradi, Hossein Allah;Zandnia, Fatemeh;Hashemi, Mehrdad;Massoudi, Nilofar;Mortazavi-Tabatabaei, SA
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.sup3
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    • pp.317-321
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    • 2016
  • Detection of micrometastasis in sentinel lymph nodes (SLNs) is a very useful tool for appropriate assessment of the clinical stage of disease in breast cancer patients. Early identification of clinically relevant disease could lead to early treatment or staging approaches for breast cancer patient. Micrometastases in SLNs of women with invasive breast cancer are of great significance in this context. In this study we examined SLN biopsies considered to have small numbers of cancerous cells by real time RT-PCR. All of the samples underwent immunohistochemical staining for cytokeratin for confirmation of the presence or absence of micrometastases. BUB1b expression assay of selected patients with and without metastasis showed overexpression in the former, but not in normal breast and lymph node tissue. Our results may be taken into account in the discussion about the merits of routine use of molecular assessment in pathogenetic studies of SLNs.

miR-19a Promotes Cell Growth and Tumorigenesis through Targeting SOCS1 in Gastric Cancer

  • Qin, Shuang;Ai, Fang;Ji, Wei-Fang;Rao, Wang;Zhang, He-Cheng;Yao, Wen-Jian
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.835-840
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    • 2013
  • Accumulating evidence has shown that microRNAs are involved in cancer development and progression. However, it remains unknown about the potential role of miR-19a in the pathogenesis of gastric cancer. Here, we report that suppressor of cytokine signaling 1 (SOCS1) is a novel target of miR-19a in gastric cancer cells and that miR-19a expression is inversely correlated with SOCS1 expression in gastric cancer cells and a subset of gastric cancer tissues. Ectopic expression of miR-19a dramatically promoted proliferation and tumorigenicity of gastric cancer cells both in vitro and in vivo. Moreover, we showed that silencing of SOCS1 promoted cell growth and colony formation resembling that of miR-19a overexpression, whereas re-introduction of SOCS1 (without the 3'-UTR) attenuated the pro-tumorigenic functions. Taken together, our findings suggest that the SOCS1 gene is a direct target of miR-19a, which functions as an oncogenic miRNA in gastric cancer by repressing the expression of tumor suppressor SOCS1.

Targeting Nrf2-Mediated Gene Transcription by Triterpenoids and Their Derivatives

  • Loboda, Agnieszka;Rojczyk-Golebiewska, Ewa;Bednarczyk-Cwynar, Barbara;Zaprutko, Lucjusz;Jozkowicz, Alicja;Dulak, Jozef
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.499-505
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    • 2012
  • Chemoprevention represents a strategy designed to protect cells or tissues against various carcinogens and carcinogenic metabolites derived from exogenous or endogenous sources. Recent studies indicate that plant-derived triterpenoids, like oleanolic acid, may exert cytoprotective functions via regulation of the activity of different transcription factors. The chemopreventive effects may be mediated through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor. Activation of Nrf2 by triterpenoids induces the expression of phase 2 detoxifying and antioxidant enzymes such as NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) - proteins which can protect cells or tissues against various toxic metabolites. On the other hand, inhibition of other transcription factors, like NF-${\kappa}B$ leads to the decrease in the pro-inflammatory gene expression. Moreover, the modulation of microRNAs activity may constitute a new mechanism responsible for valuable effects of triterpenoids. Recently, based on the structure of naturally occurring triterpenoids and with involvement of bioinformatics and computational chemistry, many synthetic analogs with improved biological properties have been obtained. Data from in vitro and in vivo experiments strongly suggest synthetic derivatives as promising candidates in the chemopreventive and chemotherapeutic strategies.