• 한국어병학회지
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• 제33권1호
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• pp.35-43
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• 2020

Hypoxia is a serious problem in the marine ecosystem causing a decline in aquatic resources. MicroRNAs (miRNAs) regulate the expression of genes through binding to the corresponding sequences of their target mRNAs. Especially, miRNAs in the cytoplasm can be secreted into body fluids, which called circulating miRNAs, and the availability of circulating miRNAs as biomarkers for hypoxia has been demonstrated in mammals. However, there has been no report on the hypoxia-mediated changes in the circulating miRNAs in fish. miR-210 is known as the representative hypoxia-responsive circulating miRNA in mammals. To know whether fish miR-210 also respond to hypoxia, we analyzed the change of circulating miR-210 quantity in the serum of olive flounder (Paralichthys olivaceus) in response to hypoxia. The expression of hypoxia related genes, hypoxia inducible factor 1α (HIF-1α) and the heat shock protein 90α (HSP90α) was also analyzed. Similar to the reports from mammals, miR-210-5p and miR-210-3p were significantly increased in the serum of olive flounder in response to hypoxia, suggesting that circulating miR-210 levels in the serum can be used as a noninvasive prognostic biomarker for fish suffered hypoxia. The target genes of miR-210 were related to various biological processes, which explains the major regulatory role of miR-210 in response to hypoxia. The expression of HIF-1α and HSP90α in the tissues was also up-regulated by hypoxia. Considering the critical role of HIF-1α in miR-210 expression and HSP90 in miRNAs function, the present up-regulation of HIF-1α and HSP90α might be related to the increase of circulatory miR-210, and the interaction mechanism among HIF-1α, HSP90α, and hypoxia-responsive microRNAs in fish should be further studied.

• Molecules and Cells
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• 제40권4호
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• pp.291-298
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• 2017

MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes posttranscriptionally. Past studies have reported that miR-210 is up-regulated in many cancers including cervical cancer, and plays a pleiotropic role in carcinogenesis. However, its role in regulating response towards anti-cancer agents has not been fully elucidated. We have previously reported that the natural compound 1'S-1'-acetoxychavicol acetate (ACA) is able to induce cytotoxicity in various cancer cells including cervical cancer cells. Hence, this study aims to investigate the mechanistic role of miR-210 in regulating response towards ACA in cervical cancer cells. In the present study, we found that ACA down-regulated miR-210 expression in cervical cancer cells, and suppression of miR-210 expression enhanced sensitivity towards ACA by inhibiting cell proliferation and promoting apoptosis. Western blot analysis showed increased expression of mothers against decapentaplegic homolog 4 (SMAD4), which was predicted as a target of miR-210 by target prediction programs, following treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to sequences in 3'UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression increased when miR-210 expression was suppressed. Lastly, we demonstrated that overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing effects of ACA. Taken together, our results demonstrated that down-regulation of miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting SMAD4. These findings suggest that combination of miRNAs and natural compounds could provide new strategies in treating cervical cancer.

• 생명과학회지
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• 제27권7호
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• pp.767-782
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• 2017

MicroRNA는 인체 지방 유래 중간엽 줄기세포(hADSC)의 분화와 증식을 조절할 수 있으나 hADSC에서 miR-200a와 miR210의 역할은 아직까지 보고된 바가 없다. 표적 mRNA의 3' UTR 에 결합할 수 있는 construct를 이용한 luciferase assay를 통하여 microRNA가 직접적으로 표적 mRNA에 결합하는 것을 확인 하였다. hADSC에서 miR-200a 과발현은 ZEB2의 발현 감소를 통해 hADSC의 분화와 증식을 증가시키는 것을 확인할 수 있었으며, miR210의 과발현은 IGFBP3의 발현 감소를 통해 hADSC의 증식을 감소시키는 반면, 분화는 증가시키는 것을 확인 할 수 있었다. hADSC에서 miR210의 발현 억제는 표적유전자의 발현을 증가시킴으로써 hADSC의 증식을 증가시키는 반면, 분화를 억제시키는 것을 확인할 수 있었다. luciferase assay통하여 microRNA-200a/210의 과발현이 대조군에 비해 표적 유전자인 ZEB2/ IGFBP3의 luciferase 활성화를 감소시키는 것을 확인하였으며, hADSC에서 ZEB2/ IGFBP3 발현 억제는 microRNA-200a/210 과발현과 유사한 효과를 나타내는 것을 확인할 수 있었다. 이러한 결과는 microRNA-200a/210가 hADSC의 분화와 증식을 각각의 표적 유전자인 ZEB2/ IGFBP3을 통해 조절한다는 것을 나타낸다.

• Molecules and Cells
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• 제43권5호
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• pp.438-447
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• 2020

The aim of this study was to explore the role of IL-6-miR-210 in the regulation of Tregs function and atrial fibrosis in atrial fibrillation (AF). The levels of interleukin (IL)-6 and IL-10 in AF patients were detected by using ELISA. Proportions of Treg cells were detected by fluorescence activated cell sorting analysis in AF patients. The expression of Foxp3, α-SMA, collagen I and collagen III were determined by western blot. The atrial mechanocytes were authenticated by vimentin immunostaining. The expression of miR-210 was performed by quantitative real-time polymerase chain reaction (qRT-PCR). TargetScan was used to predict potential targets of miR-210. The cardiomyocyte transverse sections in AF model group were observed by H&E staining. The myocardial filaments were observed by masson staining. The level of IL-6 was highly increased while the level of IL-10 (Tregs) was significantly decreased in AF patients as compared to normal control subjects, and IL-6 suppressed Tregs function and promoted the expression of α-SMA, collagen I and collagen III. Furthermore, miR-210 regulated Tregs function by targeting Foxp3, and IL-6 promoted expression of miR-210 via regulating hypoxia inducible factor-1α (HIF-1α). IL-6-miR-210 suppresses regulatory T cell function and promotes atrial fibrosis by targeting Foxp3.

• BMB Reports
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• 제42권8호
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• pp.493-499
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• 2009

MicroRNAs (miRs) are a family of small noncoding RNAs that regulate gene expression by targeting mRNAs in a sequence specific manner, inducing translational repression or mRNA degradation. In this paper we have first analyzed by microarray the miR-profile in erythroid precursor cells from one normal and two thalassemic patients expressing different levels of fetal hemoglobin (one of them displaying HPFH phenotype). The microarray data were confirmed by RT-PCR analysis, and allowed us to identify miR-210 as an highly expressed miR in the erythroid precursor cells from the HPFH patient. When RT-PCR was performed on mithramycin-induced K562 cells and erythroid precursor cells, miR-210 was found to be induced in time-dependent and dose-dependent fashion, together with increased expression of the fetal $\gamma$-globin genes. Altogether, the data suggest that miR-210 might be involved in increased expression of $\gamma$-globin genes in differentiating erythroid cells.

• 대한본초학회지
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• 제34권6호
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• pp.71-78
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• 2019

Objective : The purpose of the study was to identify expression profiling of miRNAs associated with cancers after treating allergen-removed Rhus Verniciflua Stokes and allergen-removed Rhus Verniciflua Stokes fumigaed Angelica gigas on leukemia cell lines. Methods : miRNA expression has been analyzed using miRNA array method through denaturation and hybridization after isolating the total RNA from leukemic cell line treated with 100 ㎍/㎖ of aRVS and aRVS-A each. Microarray expressions were interpreted as 'significant' on miRNAs when decreased less than 0.5 fold or increased more than 1.5 fold compared with the control group. Results : Among 158 miRNAs in total, 32 miRNAs were significantly presented in miRNAs expression. miRNA has been activated with a variety of genes for predicted targets, and the overexpressed miRNAs were categorized according to proliferation and metastasis of cancer in this study. The findings were reported that seven miRNAs (let-7b, miR-193a-5p, 296-3p, 26a, 22, 124a, 92b) showed significant expressions on proliferation and growth, seven miRNAs (miR-193a-5p, 26a, 200c, 183, 124a, 198, 210) presented meaningful expressions on invasion and metastasis, two miRNAs (let-7b, miR-210) were highly expressed on angiogenesis, five miRNAs (let-7b, miR-26a, 181d, 181c, 296-5p) related with apoptosis, and six miRNAs (let-7b, miR-200c, 183, 370, 124a, 191) were associated with prognosis of cancer and early diagnostic factors for cancer. Conclusion : The mechanism of miRNA takes a role in diagnosis, treatment, and prognotic factors for cancer as well. This study suggested that further detailed research on overexpression of specific miRNA should be carried out continuously in the future.

• 섬유기술과 산업
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• 제12권3호
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• pp.210-213
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• 2008

• Molecules and Cells
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• 제40권3호
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• pp.202-210
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• 2017

The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor $(TNF)-{\alpha}$. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship. Chromatin immunoprecipitation was used to identify the combination of $NF-{\kappa}B$ and miR-503. We found that overexpression of NS5A inhibited $TNF-{\alpha}$-induced hepatocellular apoptosis via regulating miR-503 expression. The cell viability of the $TNF-{\alpha}$ induced Hep-mock cells was significantly less than the viability of the $TNF-{\alpha}$ induced Hep-NS5A cells, which demonstrates that NS5A inhibited $TNF-{\alpha}$-induced HepG2 cell apoptosis. Under $TNF-{\alpha}$ treatment, miR-503 expression was decreased and cell viability and B-cell lymphoma 2 (bcl-2) expression were increased in the Hep-NS5A cells. Moreover, the luciferase reporter gene experiment verified that bcl-2 was a direct target of miR-503, NS5A inhibited $TNF{\alpha}$-induced $NF-{\kappa}B$ activation and $NF-{\kappa}B$ regulated miR-503 transcription by combining with the miR-503 promoter. After the Hep-NS5A cells were transfected with miR-503 mimics, the data indicated that the mimics could reverse $TNF-{\alpha}$-induced cell apoptosis and blc-2 expression. Collectively, our findings suggest a possible molecular mechanism that may contribute to HCV treatment in which NS5A inhibits $NF-{\kappa}B$ activation to decrease miR-503 expression and increase bcl-2 expression, which leads to a decrease in hepatocellular apoptosis.

• Tuberculosis and Respiratory Diseases
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• 제67권5호
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• pp.413-421
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• 2009

Background: MicroRNAs (miRNAs) play an important role in the regulation of cell proliferation, apoptosis, development and differentiation. Several studies have shown that aberrant expression of miRNAs is involved in cancer development and progression by regulating the expression of proto-oncogenes or tumor suppressor genes. In this study, we investigated miRNA expression profiles in Korean patients with non-small cell lung cancer (NSCLC). Methods: We performed miRNA microarray analysis containing 60~65 bp oligonucleotide probes representing human 318 miRNAs and validated the results of the microarray with Northern blot analysis or quantitative RT-PCR. Next, we examined the correlation between miRNA expression and the target gene transcriptional profile using a human whole-genome-expression microarray. Results: We showed that 35 miRNAs were expressed differentially in the NSCLCs and corresponding non-malignant lung tissues. We showed that 35 miRNAs were expressed differentially in the NSCLCs and corresponding nonmalignant lung tissues. Thirteen of the 35 differentially expressed miRNAs were newly identified in the present study. Of the 35 miRNAs, 2 (miR-371 and miR-210) were over-expressed in lung cancers, and 33 miRNAs, including miR-145, were under-expressed in lung cancers. miR-99b expression consistently showed a negative correlation with FGFR3 expression. Conclusion: Albeit a small number of patients were examined, these results suggest that miRNA expression profiles in Korean lung cancers may be somewhat different from the expression profiles reported on lung cancers in Western populations. The findings suggest that miR-99b might be a tumor suppressor through its up-regulation of FGFR3.

• 미생물학회지
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• 제54권1호
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• pp.81-83
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• 2018

Neisseria 속 균주 KEM232는 사람 평활면 치아우식 부위로부터 분리하였다. 균주 KEM232의 유전체는 G + C 비율이 58.5%, 2,369개의 유전자와 2,210개의 단백질 코딩 유전자, 108개의 위유전자, 51개의 RNA 유전자 그리고 한 개의 CRISPR array를 포함한 단일 원형 염색체로 구성되었으며 그 크기는 2,371,912 bp였다. 균주 KEM232의 최 근연종은 Neisseria baciliformis 로서 두 균주 사이의 16S rRNA 유전자 염기서열의 유사도는 96.8% 그리고 유전체의 평균 염기 동일성은 84%였다.