• 제목/요약/키워드: MicroRNAs (miRNA)

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Identification of Genes and MicroRNAs Involved in Ovarian Carcinogenesis

  • Wan, Shu-Mei;Lv, Fang;Guan, Ting
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.3997-4000
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    • 2012
  • MicroRNAs (miRNAs) play roles in the clinic, both as diagnostic and therapeutic tools. The identification of relevant microRNAs is critically required for ovarian cancer because of the prevalence of late diagnosis and poor treatment options currently. To identify miRNAs involved in the development or progression of ovarian cancer, we analyzed gene expression profiles downloaded from Gene Expression Omnibus. Comparison of expression patterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 508 genes that were commonly up-regulated and 1331 genes that were down-regulated in the cancer specimens. Function annotation of these genes showed that most of the up-regulated genes were related to cell cycling, and most of the down-regulated genes were associated with the immune response. When these differentially expressed genes were mapped to MiRTarBase, we obtained a total of 18 key miRNAs which may play important regulatory roles in ovarian cancer. Investigation of these genes and microRNAs should help to disclose the molecular mechanisms of ovarian carcinogenesis and facilitate development of new approaches to therapeutic intervention.

Identification of Candidate Porcine miRNA-302/367 Cluster and Its Function in Somatic Cell Reprogramming

  • Son, Dong-Chan;Hwang, Jae Yeon;Lee, Chang-Kyu
    • Reproductive and Developmental Biology
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    • 제38권2호
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    • pp.79-84
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    • 2014
  • MicroRNAs (miRNAs) are approximately 22 nucleotides of small noncoding RNAs that control gene expression at the posttranscriptional level through translational inhibition and destabilization of their target mRNAs. The miRNAs are phylogenetically conserved and have been shown to be instrumental in a wide variety of key biological processes including cell cycle regulation, apoptosis, metabolism, imprinting, and differentiation. Recently, a paper has shown that expression of the miRNA-302/367 cluster expressed abundantly in mouse and human embryonic stem cells (ESCs) can directly reprogram mouse and human somatic cells to induced pluripotent stem cells (iPSCs) efficiently in the absence of any of the four factors, Oct4, Sox2, c-Myc, and Klf4. To apply this efficient method to porcine, we analyzed porcine genomic sequence containing predicted porcine miRNA-302/367 cluster through ENSEMBL database, generated a non-replicative episomal vector system including miRNA-302/367 cluster originated from porcine embryonic fibroblasts (PEF), and tried to make porcine iPSCs by transfection of the miRNA-302/367 cluster. Colonies expressing EGFP and forming compact shape were found, but they were not established as iPSC lines. Our data in this study show that pig miRNA-302/367 cluster could not satisfy requirement of PEF reprogramming conditions for pluripotency. To make pig iPSC lines by miRNA, further studies on the role of miRNAs in pluripotency and new trials of transfection with conventional reprogramming factors are needed.

miRNA, PPI, Disease 정보의 통합 모델 설계 (Integrated Model design of miRNA, PPI and Disease Information)

  • 하경식;임진묵;김홍기
    • 한국정보과학회:학술대회논문집
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    • 한국정보과학회 2012년도 한국컴퓨터종합학술대회논문집 Vol.39 No.1(B)
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    • pp.492-494
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    • 2012
  • MicroRNAs(miRNAs)는 mRNA의 발현량을 조절하여 단백질 생성량에 영향을 주는 것으로 잘 알려져있다. miRNA의 데이터베이스는 실험으로 증명된 결과를 중심으로 구성되어 있다. 하지만 miRNA 데이터베이스는 miRNA가 대상으로 하는 유전자 정보에 초점을 맞추고 있어서 그 이상의 질병정보를 얻기에는 어려움이 있다. 본 논문에서는 miRNA와 Protein-Protein Interaction(PPI) 통합 모델을 설계하여 miRNA의 의미적 확장 방법을 제시하고 있다. 또한 Online Mendelian Inheritance in Man(OMIM)을 이용한 miRNA, PPI, 관련 질병, 질병 표준화 관계의 확장방법을 찾아보았다. 이러한 접근 방법은 이형 데이터베이스를 연결하여 하나의 생물학적 시야를 제공할 수 있을 것으로 기대된다.

miRNA, PPI, 질병 정보를 이용한 마이크로어레이 데이터 통합 모델 설계 (Integrated Model Design of Microarray Data Using miRNA, PPI, Disease Information)

  • 하경식;임진묵;김홍기
    • 한국지능시스템학회논문지
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    • 제22권6호
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    • pp.786-792
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    • 2012
  • 마이크로어레이는 수만 가지 이상의 DNA 또는 RNA를 기판위에 배열해 놓은 것이며 이 기술을 이용하여 대량의 유전자 발현을 탐색할 수 있게 되었다. 그렇지만 마이크로어레이는 실험자가 탐색하려는 특정 표현형에 대해서 설계된 실험방법을 이용하므로 제한된 숫자의 유전자 발현만을 관찰할 수 있다. 본 논문에서는 MicroRNAs(miRNAs)와 Protein-Protein Interaction(PPI) 정보를 포함하고 있는 데이터베이스를 활용하여 마이크로어레이 데이터의 의미적 확장 방법을 제시하고자 한다. 또한 Online Mendelian Inheritance in Man(OMIM) 및 International Statistical Classification of Diseases and Related Health Problems, $10^{th}$ Revision(ICD-10)을 이용하여 질병 간 유전적 공통점 파악을 시도하였다. 이러한 접근방법을 통하여 새로운 생물학적 시각을 제공할 수 있을 것으로 기대된다.

NMR hydrogen exchange study of miR156:miR156* duplexes

  • Kim, Na-Hyun;Choi, Seo-Ree;Jin, Ho-Seong;Seo, Yeo-Jin;Lee, Joon-Hwa
    • 한국자기공명학회논문지
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    • 제23권3호
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    • pp.61-66
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    • 2019
  • RNAs exhibit distinct structural and dynamic features required for proper function. The hydrogen-bonded imino protons of RNAs are a probe of the conformational transition and dynamic feature. MicroRNAs originate from primary transcripts containing hairpin structures. The levels of mature miR156 influence the flowering time of plants. To understand the molecular mechanism of biological function of $miR156:miR156^*$ duplex, we performed hydrogen exchange study on the model RNAs mimicking two phenotypes of $miR156:miR156^*$, $miR156:miR156^*$ (m-miR156a) and $miR156:miR156^*$ (m-miR156g) duplexes. This study found that the internal bulge of m-miR156a destabilized the neighboring base-pairs, whereas the bulge structure of m-miR156g did not affect the thermal stabilities of the neighboring base-pairs.

Korean Red Ginseng extract induces angiogenesis through activation of glucocorticoid receptor

  • Sung, Wai-Nam;Kwok, Hoi-Hin;Rhee, Man-Hee;Yue, Patrick Ying-Kit;Wong, Ricky Ngok-Shun
    • Journal of Ginseng Research
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    • 제41권4호
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    • pp.477-486
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    • 2017
  • Background: Our previous studies have demonstrated that ginsenoside-Rg1 can promote angiogenesis in vitro and in vivo through activation of the glucocorticoid receptor (GR). Furthermore, microRNA (miRNA) expression profiling has shown that Rg1 can modulate the expression of a subset of miRNAs to induce angiogenesis. Moreover, Rb1 was shown to be antiangiogenic through activation of a different pathway. These studies highlight the important functions of miRNAs on ginseng-regulated physiological processes. The aim of this study was to determine the angiogenic properties of Korean Red Ginseng extract (KGE). Methods and Results: Combining in vitro and in vivo data, KGE at $500{\mu}g/mL$ was found to induce angiogenesis. According to the miRNA sequencing, 484 differentially expressed miRNAs were found to be affected by KGE. Among them, angiogenic-related miRNAs; miR-15b, -23a, -214, and -377 were suppressed by KGE. Meanwhile, their corresponding angiogenic proteins were stimulated, including vascular endothelial growth factor, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and MET transmembrane tyrosine kinase. The miRNAs-regulated signaling pathways of KGE were then found by Cignal 45-Pathway Reporter Array, proving that KGE could activate GR. Conclusion: KGE was found capable of inducing angiogenesis both in vivo and in vitro models through activating GR. This study provides a valuable insight into the angiogenic mechanisms depicted by KGE in relation to specific miRNAs.

LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a ceRNA against miR-331-3p and miR-338-3p

  • Luan, Xiaotian;Wang, Yankui
    • Journal of Gynecologic Oncology
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    • 제29권6호
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    • pp.95.1-95.17
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    • 2018
  • Objective: Cervical cancer is one of the most common malignant tumors. Our previous results showed that long non-coding RNA (lncRNA) XLOC_006390 plays an important role in cervical cancer. In this study, we have explored the mechanism of action of lncRNA XLOC_006390. Methods: LncRNA XLOC_006390 was proposed to exercise its function as a competing endogenous RNA (ceRNA), and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. Two miRNAs, miR-331-3p, and miR-338-3p, were chosen for the study. Expression of miRNAs and lncRNA in cervical cancer cells and tissues was detected by reverse transcription polymerase chain reaction. To determine the correlation, silencing of XLOC_006390, over-expression of miR-331-3p, and miR-338-3p was performed in SiHa and Caski cell lines, respectively. Results: Based on the interactive effect between miRNA and lncRNA, miR-331-3p and miR-338-3p were significantly downregulated in cervical cancer cells and tissues, and their expression levels were negatively related to that of lncRNA. Our results also showed that the expression of miR-331-3p target gene NRP2, miR-338-3p target genes PKM2, EYA2 was significantly downregulated when the XLOC_006390 was knocked down. Further, XLOC_006390 was found to facilitate cervical cancer tumorigenesis and metastasis by downregulating miR-331-3p and miR-338-3p expression. Conclusion: Taken together, our study demonstrated that XLOC_006390 may serve as a ceRNA and reversely regulates the expression of miR-331-3p and miR-338-3p, thus facilitating cervical cancer tumorigenesis and metastasis.

Serum miRNA Panel in Egyptian Patients with Chronic Hepatitis C Related Hepatocellular Carcinoma

  • Khairy, Ahmed;Hamza, Iman;Shaker, Olfat;Yosry, Ayman
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권5호
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    • pp.2699-2703
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    • 2016
  • Background: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. MicroRNAs (miRNAs) have great HCC diagnostic potential and circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. Aim: To explore the potential benefit of serum miR-126, miR-129, miR-155, miR-203 and miR-223 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related HCC. Materials and Methods: The expression of miRNA was evaluated using real-time quantitative RT-PCR in 78 serum samples (30 $treatment-na{\ddot{i}}ve$ chronic HCV, 25 post-HCV compensated cirrhosis and 23 $treatment-na{\ddot{i}}ve$ HCC cases). Results: Comparing miRNA fold changes in the HCC group vs the non HCC groups, there was significant fold decrease in miR-126 (P= 0.034), miR-129 (P= 0.006), miR-155 (P= 0.011), miR-203 (P<0.001) and miR-223 (P= 0.013). The highest AUC to differentiate HCC patients from non-HCC was 0.76 for miR-203. Conclusions: Among studied miRNAs, serum miR-203 has the highest potential as a non-invasive biomarker of HCC.

MicroRNA-23a: A Novel Serum Based Diagnostic Biomarker for Lung Adenocarcinoma

  • Lee, Yu-Mi;Cho, Hyun-Jung;Lee, Soo-Young;Yun, Seong-Cheol;Kim, Ji-Hye;Lee, Shin-Yup;Kwon, Sun-Jung;Choi, Eu-Gene;Na, Moon-Jun;Kang, Jae-Ku;Son, Ji-Woong
    • Tuberculosis and Respiratory Diseases
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    • 제71권1호
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    • pp.8-14
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    • 2011
  • Background: MicroRNAs (miRNAs) have demonstrated their potential as biomarkers for lung cancer diagnosis. In recent years, miRNAs have been found in body fluids such as serum, plasma, urine and saliva. Circulating miRNAs are highly stable and resistant to RNase activity along with, extreme pH and temperatures in serum and plasma. In this study, we investigated serum miRNA profiles that can be used as a diagnostic biomarker of non-small cell lung cancer (NSCLC). Methods: We compared the expression profile of miRNAs in the plasma of patients diagnosed with lung cancer using an miRNA microarray. The data from this assay were validated by quantitative real-time PCR (qRT-PCR). Results: Six miRNAs were overexpressed and three miRNAs were underexpressed in both tissue and serum from squamous cell carcinoma (SCC) patients. Sixteen miRNAs were overexpressed and twenty two miRNAs were underexpressed in both tissue and serum from adenocarcinoma (AC) patients. Of the four miRNAs chosen for qRT-PCR analysis, the expression of miR-23a was consistent with microarray results from AC patients. Receiver operating characteristic (ROC) curve analyses were done and revealed that the level of serum miR-23a was a potential marker for discriminating AC patients from chronic obstructive pulmonary disease (COPD) patients. Conclusion: Although a small number of patients were examined, the results from our study suggest that serum miR-23a can be used in the diagnosis of AC.

Periodontopathogen LPSs Regulate MicroRNA Expression in Human Gingival Epithelial Cells

  • Lee, Hwa-Sun;Na, Hee-Sam;Jeong, So-Yeon;Jeong, Sung-Hee;Park, Hae-Ryoun;Chung, Jin
    • International Journal of Oral Biology
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    • 제36권3호
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    • pp.109-116
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    • 2011
  • Periodontitis results from the activation of host immune and inflammatory defense responses to subgingival plaque bacteria, most of which are gram-negative rods with lipopoly-saccharides (LPSs) in their cell walls. LPSs have been known to induce proinflammatory responses and recently it was reported also that they induce the expression of microRNAs (miRNAs) in host cells. In our current study therefore, we aimed to examine and compare the miRNA expression patterns induced by the LPSs of major periodontopathogens in the human gingival epithelial cell line, Ca9-22. The cells were treated with 1 ${\mu}g$/ml of E. coli (Ec) LPS or 5 ${\mu}g$/ml of an LPS preparations from four periodontopathogens Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Fusobacterium nucleatum (Fn) for 24 h. After small RNA extraction from the treated cells, miRNA microarray analysis was carried out and characteristic expression profiles were observed. Fn LPS most actively induced miRNAs related to inflammation, followed by Aa LPS, Pi LPS, and Ec LPS. In contrast, Pg LPS only weakly activated miRNAs related to inflammation. Among the miRNAs induced by each LPS, miR-875-3p, miR-449b, and miR-520d-3p were found to be commonly up-regulated by all five LPS preparations, although at different levels. When we further compared the miRNA expression patterns induced by each LPS, Ec LPS and Pi LPS were the most similar although Fn LPS and Aa LPS also induced a similar miRNA expression pattern. In contrast, the miRNA profile induced by Pg LPS was quite distinctive compared with the other bacteria. In conclusion, miR-875-3p, miR-449b, and miR-520d-3p miRNAs are potential targets for the diagnosis and treatment of periodontal inflammation induced by subgingival plaque biofilms. Furthermore, the observations in our current study provide new insights into the inflammatory miRNA response to periodontitis.