• The Journal of the Korea Contents Association
• /
• v.19 no.11
• /
• pp.375-382
• /
• 2019

Abnormalities of trophoblast due to early inflammation in pregnancy increase the expression of CRP and affect maternal-fetal interactions, leading to preterm birth and preeclampsia. However, biomarkers related to the regulation of CRP expression have not been found. In this study, miRNA associated with increased expression of CRP was identified and their expression was analyzed to reveal biomarkers involved in the regulation mechanism of trophoblast inflammation through miRNAs. miRNAs that were predicted to regulate CRP gene expression in miRNA databases (mirna, TargetScan, MicroCosm) were screened and HTR-8/SVneo cell lines were treated with LPS (20 ng/mL) to induce inflammatory responses in vitro, with selected miR-7, miR-150, miR-186 and miR-424. The expression was analyzed by qRT-PCR. As a result, expression of CRP was significantly increased in LPS-treated trophoblast (p<0.001) and miR-150 and miR-424 expression were significantly decreased (p<0.001). Thus, miR-150 and miR-424 are involved in the regulation of CRP expression in inflammatory-induced trophoblast and may be useful for the prenatal diagnosis of inflammatory obstetric diseases.

• BMB Reports
• /
• v.50 no.4
• /
• pp.226-231
• /
• 2017

At the post-transcriptional and translational levels, microRNA (miRNA) represses protein-coding genes via seed pairing to the 3' untranslated regions (UTRs) of mRNA. Although working models of miRNA-mediated gene silencing are successfully established using miRNA transfections and knockouts, the regulatory interaction between miRNA and long non-coding RNA (lncRNA) remain unknown. In particular, how the mRNA-resembling lncRNAs with 5' cap, 3' poly(A)-tail, or coding features, are regulated by miRNA is yet to be examined. We therefore investigated the functional interaction between miRNAs and lncRNAs with/without those features, in miRNA-transfected early zebrafish embryos. We observed that the greatest determinants of the miRNA-mediated silencing of lncRNAs were the 5' cap and 3' poly(A)-tails in lncRNAs, at both the post-transcriptional and translational levels. The lncRNAs confirmed to contain 5' cap, 3' poly(A)-tail, and the canonical miRNA target sites, were observed to be repressed in the level of both RNA and ribosome-protected fragment, while those with the miRNA target sites and without 5' cap and 3' poly(A)-tail, were not robustly repressed by miRNA introduction, thus suggesting a role as a miRNA-decoy.

• Journal of Life Science
• /
• v.24 no.7
• /
• pp.798-803
• /
• 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 was increased in 3T3-L1 cells exposed to Dox in a dose-dependent manner. Cellular viability of ectopically expressed CtsD cells was also decreased. Next, we used the miRanda program to search for particular microRNA targeting CtsD. MiR-145 was selected as a putative controller for CtsD because miR-145 had a high mirSVR score. In a reporter assay, the luciferase activity of cells containing the CtsD 3'-UTR region was decreased in cells transfected with 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 CtaD could be a useful therapeutic tool for the prevention and treatment of obesity by regulating fat cell numbers.

• Journal of Veterinary Clinics
• /
• v.40 no.2
• /
• pp.164-174
• /
• 2023

Canine splenic tumors (STs) are commonly diagnosed during imaging examinations, such as in X-ray and ultrasonography examinations, suggesting their higher prevalence, especially in older dogs. Despite this high prevalence, there are no effective treatment options for STs because of the difficulties in determining therapeutic targets. However, recently, the importance of microRNAs (miRNAs) has evolved owing to their ambivalent characteristics. Biomarkers and novel therapies using miRNAs have been well-studied in human cancer research compared to canine research, except for mammary gland tumors. Therefore, this study aimed to comparatively analyze miRNA expression profiles according to malignancy and biopsy sites to identify novel therapeutic and diagnostic targets. Tissue samples were collected directly from splenic tumor masses and immersed in RNAlater solution for further analysis. To investigate differentially expressed genes (DEGs) between tumor and normal tissues, we used RNA-seq and miRNA microarray analysis. Then, functional analysis based on DEGs was conducted to sort tumor-related DEGs. We found that cfa-miR-150 was upregulated in benign tumors, whereas cfa-miR-134 was upregulated in malignant tumors. Despite limited information on canine miRNAs, we identified two potential biomarkers for the differential diagnosis of STs.

• Proceedings of the Korea Information Processing Society Conference
• /
• 2008.05a
• /
• pp.433-434
• /
• 2008

기존의 실험을 통한 전통적인 생물학의 연구와는 달리, 미세 RNA (microRNA)의 연구에 있어 컴퓨터를 통한 프로그램 개발과 정보기술의 이용은 필수 불가결한 요소가 되었다. 컴퓨터를 바탕으로 한 대부분의 연구는 미세 RNA를 발현하는 유전자와 미세 RNA의 타겟 (target)을 예측하는 두가지 분야로 나누어 이루어지고 있다. 본 연구에서는 미세 RNA의 타겟을 예측하는 프로그램 개발시 이용되는 몇 가지 원칙들과 그 원칙들의 문제점을 서술하며, 현재 인터넷상에서 이용 가능한 프로그램들을 소개한다. 또한 컴퓨터를 통해 예측된 미세 RNA 의 타겟을 실험을 통해 검증하는 방법에 대해 논한다.

• Journal of Ginseng Research
• /
• v.45 no.6
• /
• pp.754-762
• /
• 2021

Background: Ginsenoside Rh2, a major saponin derivative in ginseng extract, is recognized for its anti-cancer activities. Compared to coding genes, studies on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) that are regulated by Rh2 in cancer cells, especially on competitive endogenous RNA (ceRNA) are sparse. Methods: LncRNAs whose promoter DNA methylation level was significantly altered by Rh2 were screened from methylation array data. The effect of STXBP5-AS1, miR-4425, and RNF217 on the proliferation and apoptosis of MCF-7 breast cancer cells was monitored in the presence of Rh2 after deregulating the corresponding gene. The ceRNA relationship between STXBP5-AS1 and miR-4425 was examined by measuring the luciferase activity of a recombinant luciferase/STXBP5-AS1 plasmid construct in the presence of mimic miR-4425. Results: Inhibition of STXBP5-AS1 decreased apoptosis but stimulated growth of the MCF-7 cells, suggesting tumor-suppressive activity of the lncRNA. MiR-4425 was identified to have a binding site on STXBP5-AS1 and proven to be downregulated by STXBP5-AS1 as well as by Rh2. In contrast to STXBP5-AS1, miR-4425 showed pro-proliferation activity by inducing a decrease in apoptosis but increased growth of the MCF-7 cells. MiR-4425 decreased luciferase activity from the luciferase/STXBP5-AS1 construct by 26%. Screening the target genes of miR-4425 and Rh2 revealed that Rh2, STXBP5-AS1, and miR-4425 consistently regulated tumor suppressor RNF217 at both the RNA and protein level. Conclusion: LncRNA STXBP5-AS1 is upregulated by Rh2 via promoter hypomethylation and acts as a ceRNA, sponging the oncogenic miR-4425. Therefore, Rh2 controls the STXBP5-AS1/miR-4425/RNF217 axis to suppress breast cancer cell growth.

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

• BMB Reports
• /
• v.51 no.8
• /
• pp.406-411
• /
• 2018

Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associated with cell apoptosis, growth and migration. For animal studies, the mice injected with U87 cells were exposed to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence of exosomal miRNA on the progress of glioma. Based on our results, we propose a new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs could be used to modulate tumor progress as the anticancer vehicles.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.18
• /
• pp.7489-7497
• /
• 2014

MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.

• Journal of Life Science
• /
• v.27 no.7
• /
• pp.767-782
• /
• 2017

MicroRNAs control the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs). However, the role of miR-200a and miR210 on the osteogenic differentiaton of hADSCs has not been determined. hADSCs were isolated from human adipose tissues. Direct binding of mircoRNA to target mRNAs was determined by luciferase assay of the constructs containing putative microRNA binding sites within 3' untranslated region of target mRNAs. Overexpression of miR-200a increased the proliferation and osteogenic differentiation of hADSCs, while causing downregulation of the levels of ZEB2. Inhibition of miR-200a with antisense RNAs inhibited the proliferation and osteogenic differentiation of hADSCs. Overexpression of miR-210 was found to inhibit the proliferation of hADSCs but increase the osteogenic differentiation, while causing downregulation of the levels of IGFBP3. Inhibition of miR-210 with antisense RNAs increased the proliferation but inhibited the osteogenic differentiation of hADSCs. Analysis of the luciferase activity of the constructs containing the miR-200a target site within the ZEB2 3' region and the miR-210 target site within the IGFBP3 3' region revealed lower activity in the miR-200a- or miR-210-transfected hADSCs than in control miRNA-transfected hADSCs. Downregulation of ZEB2 or IGFBP3 in the hADSCs showed similar effects on both their proliferation and osteogenic differentiation with that of miR-200a and miR-210 overexpression, respectively. The results of the current study indicate that miR-200a and miR-210 regulate the osteogenic differentiation and proliferation of hADSCs through the direct targeting of IGFBP3 and ZEB2, respectively.