• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.829-834
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• 2013

Background: MicroRNAs are noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was to determine the role of microRNA-21 in cholangiocarcinomas and its relationship to cholangiocarcinoma RBE cell capacity for invasion and metastasis. Methods: MicroRNA-21 expression was investigated in 41 cases of cholangiocarcinoma samples by in situ hybridization and real-time PCR. Influence on cholangiocarcinoma cell line invasion and metastasis was analyzed with microRNA-21 transfected cells. In addition, regulation of reversion-inducing-cysteine-rich protein with kazal motifs (RECK) by microRNA-21 was elucidated to identify mechanisms. Results: In situ hybridization and real-time quantitative PCR results for patients with lymph node metastasis or perineural invasion showed significantly high expression of microRNA-21 (P<0.05). There was a dramatic decrease in cholangiocarcinoma cell line invasion and metastasis ability after microRNA-21 knockdown (P<0.05). However, overexpression significantly increased invasion and metastasis (P<0.05). Real-time PCR and Western-blot analysis showed that microRNA-21 could potentially inhibit RECK expression in RBE cells. Survival analysis showed that patients with higher expression levels of microRNA-21 more often had a poor prognosis (P<0.05). Conclusions: MicroRNA-21 may play an important role in cholangiocarcinoma invasion and metastasis, suggesting that MicroRNA-21 should be further evaluated as a biomarker for predicting cholangiocarcinoma prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3437-3445
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• 2016

Background: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be down-regulated in clinical samples, most likely due to the post-transcriptional modification by microRNAs. Targeted genes would be up-regulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors. Materials and Methods: MicroRNA software predicted that miR-21 targets VCL while miR-29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalin-fixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE-1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels. Results: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down-regulated while CX3CL1 was up-regulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly upregulated while CX3CL1 mRNA was significantly down-regulated compared to the RWPE-1 case. Conclusions: The down-regulation of VCL in FFPE specimens is most likely regulated by miR-21 based on the in vitro evidence but the exact mechanism of how miR-21 can regulate VCL is unclear. Up-regulated in CaP, CX3CL1 was found not regulated by miR-29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNA-mRNA interactions may provide additional knowledge for individualized study of cancers.

• Molecules and Cells
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• v.46 no.1
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• pp.21-32
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• 2023

MicroRNAs (miRNAs) play cardinal roles in regulating biological pathways and processes, resulting in significant physiological effects. To understand the complex regulatory network of miRNAs, previous studies have utilized massivescale datasets of miRNA targeting and attempted to computationally predict the functional targets of miRNAs. Many miRNA target prediction tools have been developed and are widely used by scientists from various fields of biology and medicine. Most of these tools consider seed pairing between miRNAs and their mRNA targets and additionally consider other determinants to improve prediction accuracy. However, these tools exhibit limited prediction accuracy and high false positive rates. The utilization of additional determinants, such as RNA modifications and RNA-binding protein binding sites, may further improve miRNA target prediction. In this review, we discuss the determinants of functional miRNA targeting that are currently used in miRNA target prediction and the potentially predictive but unappreciated determinants that may improve prediction accuracy.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.150-157
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• 2004

microRNA (miRNA)는 21-25 nucleotide (nt)의 single-stranded RNA 분자로서 mRNA의 3' untranslated region (3' UTR)에 상보적으로 결합하여 유전자 발현을 제어하는 새로운 조절물질이다. 지금까지 실험을 통해 수백 개의 miRNA가 알려져 있으나, miRNA에 의해 조절되는 target 유전자는 실험상의 어려움으로 아직까지 거의 알려지지 않았다. miRNA는 서열의 길이가 짧고 target과 느슨한 상보적 결합을 하기 때문에 기존의 서열 비교 방법으로 miRNA의 target을 찾는 것은 쉬운 일이 아니다. 본 논문은 신경망을 이용하여 Caenorhabditis elegans mRNA의 3' UTR에서 miRNA가 결합하는 영역을 예측하였다. 신경망은 복잡한 비선형 데이터를 잘 분리해내고 불완전하고 잡음이 많은 입력에 강하기 때문에 miRNA target 예측에 적합하다. miRNA와 mRNA의 결합 영역을 다양하게 분석하였고 민감도 0.59, 특수도 0.99의 성능을 갖는 신경망을 구현하였다. 신경망 입력 값을 달리하여 각각의 특성이 결과에 미치는 영향을 분석하였고 기존 예측 방법에 의한 결과와 비교하여 성능을 평가하였다.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.292-297
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• 2015

Research of thyroid cancer, liver cancer, and lung cancer has been reported in Korea. However microRNA research of multiple myeloma has never been reported. Hence we intended to confirm whether microRNA can be utilized as a diagnostic marker to patients of multiple myeloma. We also intended to evaluate whether microRNA can be detected in paraffin-embedded tissue (FFPE). This research was conducted targeting 8 samples from patients of multiple myeloma who do not have any other diseases, and 2 control samples. From January 2010 to July 2012, we selected miR-15a, miR-16, miR-21, miR-181a and miR-221 as microRNA target genes. It was decided that for a sample to be significant, the results should show values more than 1.5 or less than -1.5. Our findings of fold change were highly significant in miR-15a with a value of 37.5% (3/8). From these studies, we learned that miR-15a is useful with westerners. miR-221, on the other hand, shows conflicts with westerners, so more research will be needed in this area. In addition, it was confirmed that microRNA can be detected in paraffin embedded tissue (FFPE).

• BMB Reports
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• v.47 no.8
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• pp.417-423
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• 2014

MicroRNAs (miRNAs) are a large family of post-transcriptional regulators, which are 21-24 nt in length and play a role in a wide variety of biological processes in eukaryotes. The past few years have seen rapid progress in our understanding of miRNA biogenesis and the mechanism of action, which commonly entails a combination of target degradation and translational repression. The target degradation mediated by Argonaute-catalyzed endonucleolytic cleavage exerts a significant repressive effect on target mRNA expression, particularly during rapid developmental transitions. This review outlines the current understanding of the mechanistic aspects of this important process and discusses several different experimental approaches to identify miRNA cleavage targets.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9059-9064
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• 2014

MicroRNAs (miRNAs) are ubiquitously expressed small, non-coding RNAs that negatively regulate gene expression at a post transcriptional/translational level. They have emerging as playing crucial roles in cancer at all stages ranging from initiation to metastasis. As a tumor suppressor miRNA, aberrant expression of microRNA-29b (miR-29b) has been detected in various types of cancer, and its disturbance is related with tumor development and progression. In this review, we summarize the latest findings with regard to the tumor suppressor signatureof miR-29b and its regulatory mechanisms. Our review highlights the diverse relationships between miR-29b and its target genes in malignant tumors.

• Journal of Web Engineering
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• v.14 no.13
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• pp.2684-2695
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• 2022

The aim of the present study was to examine the effect of green tea extract containing Piper retrofractum fruit (GTP) on dextran-sulfate-sodium (DSS)-induced colitis, the regulatory mechanisms of microRNA (miR)-21, and the nuclear factor-κB (NF-κB) pathway. Different doses of GTP (50, 100, and 200 mg/kg) were administered orally once daily for 14 days, followed by GTP with 3% DSS for 7 days. Compared with the DSS-treated control, GTP administration alleviated clinical symptoms, including the disease activity index (DAI), colon shortening, and the degree of histological damage. Moreover, GTP suppressed miR-21 expression and NF-κB activity in colon tissue of DSS-induced colitis mice. The mRNA levels of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were downregulated by GTP. Colonic nitric oxide (NO) and prostaglandin E2 (PGE2) production, and myeloperoxidase (MPO) activity were also lowered by GTP. Taken together, our results revealed that GTP inhibits DSS-induced colonic inflammation by suppressing miR-21 expression and NF-κB activity, suggesting that it may be used as a potential functional material for improving colitis.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.2
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• pp.197-204
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• 2018

Multiple myeloma (MM) is the leading cause of death among hematologic neoplasms. Recently, microRNA has been reported to be useful in the diagnosis of multiple myeloma. This study examined whether miR-221 could be used as a diagnostic marker for multiple myeloma. The study was performed on 20 patients with multiple myeloma without any other hematological diseases. MicroRNA extraction was performed using formalin-fixed paraffin-embedded (FFPE) tissues obtained from the bone marrow of patients with multiple myeloma. miR-15a, miR-16, miR-21, miR-181a, and miR-221 were selected as the microRNA target genes for multiple myeloma. The significance of microRNA was based on a fold change of <1.5. To quantify the fold changes, data normalized to the human gene, SNORD43, were used as the values of the patient group. Fold change values greater than 1.5 were defined as "overexpression", whereas values less than -1.5 were defined as "underexpression". Of note, 65.0% (13/20) of samples showed significant "overexpression" in the levels of miR-221 expression and plasma cells with a group of more and less than 30% in MM patients did not show any significance of plasma cell (P<0.05). The results of other studies showing a correlation between the expression of miR-221 and MM in Caucasians were confirmed. These results suggest that miR-221 may be a useful indicator for diagnosing patients with MM. In conclusion, miR-221 is useful in the diagnosis and determining the prognosis of multiple myeloma in Koreans.

• International Journal of Molecular Medicine
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• v.43 no.6
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• pp.2319-2328
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• 2019

Exosomes serve important functions in cell-to-cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood-derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR-21 using a human peripheral blood derived-exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL-1 cells, miR-21 expression was successfully regulated by treatment with human peripheral blood derived-exosomes loaded with an miR-21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR-21 mimic- or inhibitor-loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR-21 mimic- or inhibitor-loaded exosomes. Furthermore, miR-21 mimic-loaded exosomes enhanced fibrosis, whereas miR-21 inhibitor-loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA-loaded human peripheral blood derived-exosomes may be used as a therapeutic tool for cardiac diseases.