• 한국콘텐츠학회논문지
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• 제19권11호
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• pp.375-382
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• 2019

임신 초기 염증으로 인한 영양막세포의 기능 이상은 C-reactive protein (CRP)의 발현을 증가시켜 산모와 태아의 상호작용에 영향을 미침으로써, 조산 및 자간전증 등을 유발한다. 그러나, CRP 발현 조절과 관련된 생체표지자 발굴 및 개발은 미흡한 실정이다. 본 연구는 염증이 유발된 영양막세포에서 증가된 CRP 발현과 관련된 miRNA를 발굴 및 그 발현을 분석함으로써, miRNA를 통해 영양막세포 염증 조절 기전에 관여하는 생체표지자를 밝히고자 한다. miRNA 데이터베이스(mirna, TargetScan, MicroCosm)에서 공통적으로 CRP 유전자 발현을 조절할 것으로 예측되는 miR-7, miR-150, miR-186, 그리고 miR-424를 선별하여 HTR-8/SVneo에 LPS (20ng/mL)를 처리하여 in vitro 상에서 염증 반응을 유도하였다. 각각의 miRNAs의 발현을 qRT-PCR 방법으로 비교 분석하였다. 그 결과, LPS 처리된 영양막세포에서 CRP의 발현은 유의성 있게 증가되었다(p<0.001). miR-150와 miR-424는 발현이 유의성 있게 감소됨을 확인하였다(p<0.001). 따라서, 염증이 유도된 영양막세포에서의 CRP 발현을 조절하는 기전에 miR-150와 miR-424가 관여하는 것을 의미하며, 향후 염증성 산과질환의 산전 진단에 유용한 자료로 사용될 것으로 사료된다.

• Journal of Ginseng Research
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• 제40권2호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6569-6572
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• 2013

In cervical cancer, one of the most common malignant tumors in women worldwide, miR-126 has been reported to exhibit decreased expression. However, its role in cervical cancer cell proliferation and drug sensitivity has remained relatively unexplored. Here, we compared the expression of miR-126 in cervical cancer tissues (n = 20) with that in normal cervical tissue (n = 20) using quantitative RT-PCR. The viability of Siha cervical cancer cells was further measured by MTT assay after transfection with miR-126 mimic (Siha-miR-126 mimic) or microRNA mimic negative control (Siha-miR mimic NC) and after treatment with various concentrations of bleomycin (BLM). IC50s were calculated, and the survival rates (SRs) of Siha cells were calculated. miR-126 expression in cervical cancer tissue was significantly decreased compared with that in normal cervical tissue (P < 0.01). The relative SRs of Siha-miR-126 mimic cells were also significantly decreased compared with those of Siha-miR mimic NC cells at 24-96 h after transfection. The IC50 of BLM in Siha-miR-126 mimic cells ($50.3{\pm}2.02{\mu}g/mL$) was decreased compared with that in Siha-miR mimic NC cells ($70.5{\pm}4.33{\mu}g/mL$) at 48 h after transfection (P < 0.05). Finally, the SRs of Siha-miR-126 mimic cells were significantly lower than those of SihamiR mimic NC cells after cultured in medium containing 40 ${\mu}g/mL$ BLM for 24-96 h (P < 0.05). These results suggest that miR-126 is expressed at low levels in cervical cancer. Upregulation of miR-126 inhibited cervical cancer cell proliferation and enhanced the sensitivity to BLM. Thus, miR-126 may represent a novel approach to cervical cancer treatment.

• Journal of Gastric Cancer
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• 제20권2호
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• pp.212-224
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• 2020

Purpose: miR-205 is a tumor suppressor and plays an important role in tumor invasiveness. However, the role of miR-205 in human gastric cancer (GC) epithelial-mesenchymal transition (EMT) remains unclear. The aim of this study was to investigate the molecular mechanism of miR-205 in the regulation of EMT in GC invasion. Materials and Methods: Quantitative polymerase chain reaction (qPCR) was used to detect the expression of miR-205 in GC. Further, the correlation between the pathological parameters and prognosis of GC was statistically analyzed. A transwell model was used to evaluate the effect of miR-205-3p on the invasion and migration of GC cells. qPCR, western blotting, and luciferase assay were performed to analyze the relationship and target effects between miR-205-3p and the expression of zinc finger electron box binding homologous box 1 (ZEB1) and 2 (ZEB2). Results: We found that the levels of miR-205-3p were significantly lower (P<0.05) in GC tissues than in matched normal tissues. Additionally, the expression of miR-205-3p was related to the tumor invasion depth, lymph node metastasis, lymph node invasion, and tumor, node, metastasis stage. Patients with lower miR-205-3p expression levels in the tumors had a poorer prognosis. The in vitro assays indicated that miR-205-3p could affect the invasion ability and EMT of GC cells by targeting the expression of both ZEB1 and ZEB2. Conclusions: miR-205-3p promotes GC progression and affects the prognosis of patients by targeting both ZEB1 and ZEB2 to directly influence EMT.

• Progress in Superconductivity
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• 제10권1호
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• pp.6-11
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• 2008

Multi-channel magnetocardiography (MCG) has been proposed to detect ischemic heart disease because its sensitivity is quite high comparing with other conventional diagnostic tools. Especially, current map and magnetic field map of MCG provide crucial information on whether myocardiac muscles maintain the normal conduction pathway. In addition, MCG parameters derived from repolarization are useful to detect coronary artery disease. Recently, there was a study reporting that R- and T- wave amplitude are highly correlated with ischemic heart disease. In this study, we studied R- and T-wave amplitude and their ratio as well as MCG parameters. MCG data from 20 young, 20 age-matched controls, and 20 myocardial infarction (MI) patients were analyzed. As a result, MCG parameters showed significant change in MI patients comparing to those of controls. R- and T-wave amplitude of MI patients showed a feature of severe ischemic heart disease even though it was difficult to find consistent values. Further study is needed to reveal the relations between small T-wave amplitude and coronary artery disease.

• Molecular & Cellular Toxicology
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• 제5권1호
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3313-3317
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• 2012

Prostate cancer is a highly prevalent disease in older men of the western world. MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. To identify the diagnostic potential of miRNAs in prostate cancer, we downloaded the miRNA expression profile of prostate cancer from the GEO database and analysed the differentially expressed miRNAs (DE-miRNAs) in prostate cancerous tissue compared to non-cancerous tissue. Then, the targets of these DE-miRNAs were extracted from the database and mapped to the STRING and KEGG databases for network construction and pathway enrichment analysis. We identified a total of 16 miRNAs that showed a significant differential expression in cancer samples. A total of 9 target genes corresponding to 3 DE-miRNAs were obtained. After network and pathway enrichment analysis, we finally demonstrated that miR-20 appears to play an important role in the regulation of prostate cancer onset. MiR-20 as single biomarker or in combination could be useful in the diagnosis of prostate cancer. We anticipate our study could provide the groundwork for further experiments.

• Asian-Australasian Journal of Animal Sciences
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• 제33권12호
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• pp.1873-1884
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• 2020

The demand for food is increasing day by day because of the increasing global population. Therefore, meat, the easiest and largely available source of protein, needs to be produced in large amounts with good quality. The pork industry is a significant shareholder in fulfilling the global meat demands. Notably, myogenesis- development of muscles during embryogenesis- is a complex mechanism which culminates in meat production. But the molecular mechanisms which govern the myogenesis are less known. The involvement of miRNAs in myogenesis and meat quality, which depends on factors such as myofiber composition and intramuscular fat contents which determine the meat color, flavor, juiciness, and water holding capacity, are being extrapolated to increase both the quantity and quality of pork. Various kinds of microRNAs (miRNAs), miR-1, miR-21, miR22, miR-27, miR-34, miR-127, miR-133, miR-143, miR-155, miR-199, miR-206, miR-208, miR-378, and miR-432 play important roles in pig skeletal muscle development. Further, the quality of meat also depends upon myofiber which is developed through the expression of different kinds of miRNAs at different stages. This review will focus on the mechanism of myogenesis, the role of miRNAs in myogenesis, and meat quality with a focus on the pig.

• Clinical and Experimental Reproductive Medicine
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• 제36권4호
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• pp.265-274
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• 2009

목 적: 미세리보핵산 (microRNA, miR)은 전사 후 (post-transcriptional) 단계에서 목표 유전자 (target gene)의 발현을 억제하여 세포의 발달과 성장에 중요한 역할을 하는 것으로 알려져 있다. 그러나 난포의 성장과정 중의 miR 발현 양상에 대해서는 잘 알려져 있지 않다. 따라서 존 연구는 생쥐 난포의 체외배양 후 생식샘자극호르몬 (gonadotropin)과 사람융모성생식샘자극호르몬 (hCG) 첨가에 따른 난자와 난구세포에서의 miR 발현 양상을 살펴보고자 수행되었다. 연구방법: 생후 12일된 생쥐 (C57BL6)의 난소 적출 후, 전동 난포 (preantral follicle)를 분리하여 무작위로 $20\;{\mu}L$ 점적의 배양액만 있는 군 (control group), 재조합 난포자극호르몬을 첨가한 군 (FSH group), 재조합 황체형성호르몬을 첨가한 군 (LH group), FSH와 LH를 같이 첨가한 군 (FSH+LH group)으로 나누어 배양하였다. 난포가 충분히 성장하였을 때, 다시 hCG를 첨가한 군 (hCG (+) group)과 첨가하지 않은 군 (hCG (-) group)으로 나누어 hCG (-) group에서 난자와 난구세포를 각각 분리하여 RNA를 추출하였다. 36시간 후, 배란된 난자 난구세포 복합체 (cumulus oocyte complex, COC)에서 난자와 난구세포를 각각 분리하여 RNA를 추출하고, mmu--miR-16, -miR-27a, -miR-126, -miR-721 등의 miR에 대한 primer를 이용하여 실시간 중합연쇄반응을 시행하였다. 결 과: 배란율과 MII 난자 생성율은 다른 군들에 비해 FSH+LH군에서 유의하게 높았다. 각 군내의 난자와 난구세포 사이에서도 miR 발현 양상의 차이가 관찰되었다. 또한, 난자와 난구세포에서의 miR 발현 양상은 각 군간 차이가 있었으며, hCG (+)군과 hCG (-)군간에도 차이를 나타냈다. 결 론: 생쥐 난포의 체외배양 중 난자 및 난구세포에서의 miR 발현 양상은 gonadotropin의 종류 및 난자의 성숙도에 따라 다르다. 이러한 결과는 표적 유전자의 발현에 대한 추후 연구를 통한 확인이 필요할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.1047-1055
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• 2014

Background: MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive. Methodology/Principal Findings: PubMed, EMBASE, CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913, a significantly decreased risk of CRC development was observed under three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-$196a2^*T$ variant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685-0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000). As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group. Conclusions: These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 polymorphisms may contribute to susceptibility to CRC.