• Title, Summary, Keyword: microRNA

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Defining microRNA functional families through correlation analysis of microRNA microarray data (microRNA 발현 데이터의 상관관계 분석을 통한 microRNA Functional Family 탐색)

  • Nam Jin-Wu;Zhang Byoung-Tak
    • Proceedings of the Korean Information Science Society Conference
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    • pp.13-15
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    • 2006
  • microRNA는 유전자의 전사 후 과정에서 negative regulation을 담당하는 small noncoding RNA의 한 증류이다. 최근까지 330여개의 인간 microRNA가 발견되었지만 그들의 기능이 밝혀진 것은 소수에 불과하다. microRNA의 기능은 3'UTR에 불완전 상보결합을 통해 negative regulation을 받게 되는 유전자의 기능으로부터 유추되는 것이 일반적이다. 특별히 유전체상에 군집화 된 microRNA들은 하나의 전사체로부터 발현되는 것으로 판단되며, 같은 또는 관련된 기능을 하거나 같은 목표 유전자를 조절하기 위한 functional family일 가능성이 높다. 또한 이러한 functional family는 하나의 전사체로부터 발현되기 때문에, 조직별로 조건별로 같은 발현 패턴을 보여야 한다. 본 연구에서는 발현데이터로부터 microRNA functional family를 탐색하기 위해, 5개의 연구 그룹에서 공개한 조직별 microRNA 발현데이터를 표준화 작업을 거친 후 통합하고 k-nearest neighbor 알고리즘을 이용해 결측치를 보정한 후 microRNA 발현사이의 correlation을 계산한다. 이때 데이터 통합에서 생기는 문제에 robust한 결과를 얻기 위해 실제 발현데이터가 아닌 rank 데이터부터 correlation을 측정한다. 계산된 spearman ranked correlation 결과와 microRNA의 genomic coordination 정보로부터 34개의 functional family를 정의할 수 있었다.

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How to Explain the Contradiction of microRNA 200c Expression and Survival in Solid Tumors?: a Meta-analysis

  • Wang, Hui-Yu;Shen, Jie;Jiang, Chun-Ping;Liu, Bao-Rui
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3687-3690
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    • 2014
  • MicroRNA 200c is a microRNA 200 family member that plays an important role in regulation of the epithelial-to-mesenchymal transition (EMT). The prognostic value of microRNA 200c in solid tumors remains controversial because of inconsistent data. Here, we report a meta-analysis of the association of microRNA 200c expression and survival in patients with solid tumors. Pubmed was searched up to November 2013 for studies investigating microRNA 200c expression and overall survival (OS) in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) for OS were extracted from each study. Pooled HR and CIs were calculated using the Mantel-Haenszel fixed-effects models. A total of five studies evaluating colorectal cancer, gastric cancer, ovarian cancer, pancreatic cancer and endometrial cancer were included in the analysis. Data were divided into tissue microRNA 200c expression group and serum microRNA 200c expression group. The combined HRs [95%CIs] estimated for OS were 0.62 [0.42-0.91] and 2.16 [1.32-3.52] respectively. Low expression of microRNA 200c in tumor tissue and high expression of microRNA 200c in serum are associated with worse survival in solid tumors. Further study is needed to elucidate this contradiction.

MicroRNA-21 Regulates the Invasion and Metastasis in Cholangiocarcinoma and May Be a Potential Biomarker for Cancer Prognosis

  • Huang, Qiang;Liu, Lei;Liu, Chen-Hai;You, Hao;Shao, Feng;Xie, Fang;Lin, Xian-Sheng;Hu, San-Yuan;Zhang, Chuan-Hai
    • 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.

MicroRNA-146a Enhances Helicobacter pylori Induced Cell Apoptosis in Human Gastric Cancer Epithelial Cells

  • Wu, Kai;Yang, Liu;Li, Cong;Zhu, Chao-Hui;Wang, Xin;Yao, Yi;Jia, Yu-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5583-5586
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    • 2014
  • Helicobacter pylori (H. pylori) infection induces apoptosis in gastric epithelial cells, and this occurrence may link to gastric carcinogenesis. However, the regulatory mechanism of H. pylori-induced apoptosis is not clear. MicroRNA-146a has been implicated as a key regulator of the immune system. This report describes our discovery of molecular mechanisms of microRNA-146a regulation of apoptosis in human gastric cancer cells. We found that overexpression of microRNA-146a by transfecting microRNA-146a mimics could significantly enhance apoptosis, and this upregulation was triggered by COX-2 inhibition. Furthermore, we found that microRNA-146a density was positively correlated with apoptosis rates in H. pylori-positive gastric cancer tissues and intratumoral microRNA-146a density was negatively correlated with lymph node metastasis among H. pylori-positive gastric cancer patients. Understanding the important roles of microRNA-146a in regulating cell apoptosis in H. pylori infected human gastric cancer cells will contribute to the development of microRNA targeted therapy in the future.

Exosome-derived microRNA-29c Induces Apoptosis of BIU-87 Cells by Down Regulating BCL-2 and MCL-1

  • Xu, Xiang-Dong;Wu, Xiao-Hou;Fan, Yan-Ru;Tan, Bing;Quan, Zhen;Luo, Chun-Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3471-3476
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    • 2014
  • Background: Aberrant expression of the microRNA-29 family is associated with tumorigenesis and cancer progression. As transport carriers, tumor-derived exosomes are released into the extracellular space and regulate multiple functions of target cells. Thus, we assessed the possibility that exosomes could transport microRNA-29c as a carrier and correlations between microRNA-29c and apoptosis of bladder cancer cells. Materials and Methods: A total of 28 cancer and adjacent tissues were examined by immunohistochemistry to detect BCL-2 and MCL-1 expression. Disease was Ta-T1 in 12 patients, T2-T4 in 16, grade 1 in 8, 2 in 8 and 3 in 12. The expression of microRNA-29c in cancer tissues was detected by quantitative reverse transcriptase PCR (QRT-PCR). An adenovirus containing microRNA-29c was used to infect the BIU-87 human bladder cancer cell line. MicroRNA-29c in exosomes was measured by QRT-PCR. After BIU-87 cells were induced by exosomes-derived microRNA-29c, QRT-PCR was used to detect the level of microRNA-29c. Apoptosis was examined by flow cytometry and BCL-2 and MCL-1 mRNA expressions were assessed by reverse transcription-polymerase chain reaction. Western blotting was used to determine the protein expression of BCL-2 and MCL-1. Results: The expressions of BCL-2 and MCL-1 protein were remarkably increased in bladder carcinoma (p<0.05), but was found mainly in the basal and suprabasal layers in adjacent tissues. The expression of microRNA-29c in cancer tissues was negatively correlated with the BCL-2 and MCL-1. The expression level of microRNA-29c in exosomes and BIU-87 cells from the experiment group was higher than that in control groups (p<0.05). Exosome-derived microRNA-29c induced apoptosis (p<0.01). Although only BCL-2 was reduced at the mRNA level, both BCL-2 and MCL-1 were reduced at the protein level. Conclusions: Human bladder cancer cells infected by microRNA-29c adenovirus can transport microRNA-29c via exosomes. Moreover, exosome-derived microRNA29c induces apoptosis in bladder cancer cells by down-regulating BCL-2 and MCL-1.

Prediction of MicroRNA Strand Selection using Hypernetwork Model (하이퍼망 모델을 이용한 MircoRNA Strand 선택 예측)

  • Lee, Ji-Hoon;Ha, Jung-Woo;Rhee, Je-Keun;Zhang, Byoung-Tak
    • Proceedings of the Korean Information Science Society Conference
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    • pp.235-239
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    • 2010
  • MicroRNA는 RNA로 전사된 유전자와의 상보결합을 통해 유전자 발현을 억제하는 조절인자이다. MicroRNA 생성과정에서 pre-microRNA의 3' 또는 5' 부근의 strand가 선택되어 mature 시퀀스가 되고 유전자 조절에 직접 작용하게 된다. 하지만 어떤 특징을 가진 strand가 선택 되는지에 대한 정확한 메커니즘은 아직 연구되어 있지 않다. 본 논문에서는 microRNA 시퀀스 정보를 바탕으로 하이퍼망을 구성하여 strand 선택 예측 모델을 구축하였다. 실험 결과 하이퍼망 학습을 통해 microRNA strand 선택에 중요한 영향을 미치는 시퀀스 특징을 찾을 수 있었고, strand 선택을 높은 정확도로 예측할 수 있음을 확인하였다.

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Expression and Significance of MicroRNA155 in Serum of Patients with Cerebral Small Vessel Disease

  • Guo, Ying;Li, Dongxue;Li, Jiapei;Yang, Nan;Wang, Deyun
    • Journal of Korean Neurosurgical Society
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    • v.63 no.4
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    • pp.463-469
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    • 2020
  • Objective : This study aimed to investigate the changes and significance of microRNA155 levels in serum of patients with cerebral small vessel disease (CSVD). Methods : Thirty patients with CSVD who met the inclusion criteria were selected and divided into eight patients with lacunar infarction (LI) group and 22 patients with multiple lacunar infarction (MLI) combined with white matter lesions (WML) group according to the results of head magnetic resonance imaging (MRI). Thirty samples from healthy volunteers without abnormalities after head MRI examination were selected as the control group. The levels of serum microRNA155 in each group were determined by real-time polymerase chain reaction, and the correlation between microRNA155 in the serum of patients with CSVD and the increase of imaging lesions was analyzed by Spearman correlation analysis. Results : Compared with the control group, the serum microRNA155 level in the LI group, MLI combined with WML group increased, the difference was statistically significant (p<0.05); serum microRNA155 level was positively correlated with the increase of imaging lesions (p<0.05). Conclusion : The change of serum microRNA155 level in patients with CSVD may be one of its self-protection mechanisms, and the intensity of this self-protection mechanism is positively correlated with the number of CSVD lesions.

Comparison of MicroRNA Expression in Placenta-derived Mesenchymal Stem Cells and Bone Marrow-derived Stem Cells (태반유래 줄기세포와 골수유래 줄기세포에서의 마이크로RNA 발현비교)

  • Kim, Soo Hwan
    • Journal of Life Science
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    • v.24 no.11
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    • pp.1238-1243
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    • 2014
  • Mesenchymal stem cells (MSCs) have been widely used as cellular therapeutic agents. They have their own characteristic stemness, and thus, they can be used in the treatment of many chronic diseases and in anticancer therapy. MSC therapy has many advantages over chemical therapy. MSC therapy is based on self or homogeneous origin; as such, it is expected to be effective in the treatment of various diseases. In addition, microRNAs in particular have been studied for their structure and function, and they are also expected to prove effective for use as therapeutic agents in cancer or chronic diseases. MicroRNAs are largely associated with metabolism and homeostasis. Therefore, over- or under-expression of microRNAs leads to chronic diseases. Conversely, effective control of the expression of specific microRNAs reduces the risk of many chronic diseases. However, there have been no reports thus far on the synergistic effects of MSCs and microRNAs. Therefore, in this study, we examined the relationship between MSCs and microRNAs using placenta-derived MSCs (PDSCs), bone marrow-derived MSCs (BM-MSCs), and fibroblast (WI-38) cells. We studied the expression of some microRNAs in MSCs and compared the expression in each cell line and cell passage. As a result, we found that the expression of microRNA-34a was higher in PDSCs than in BM-MSCs and that the expression of microRNA-27a, 33a, 33b, and 211 was higher in BM-MSCs than in PDSCs. Therefore, we expect that each MSC line will be used as cell therapy, considering its expressed functional microRNA.

Evolutionary Optimization of Models for Mature microRNA Prediction (Mature microRNA 위치 예측 모델의 진화적 최적화)

  • Kim Jin-Han;Nam Jin-Wu;Zhang Byoung-Tak
    • Proceedings of the Korean Information Science Society Conference
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    • pp.67-69
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    • 2006
  • MicroRNA (miRNA)는 생체내에서 gene regulation에 관여하는 핵심 small RNA 중 하나이다. miRNA는 Primary miRNA, Precursor miRNA, mature miRNA의 과정으로 processing 된다. miRNA 최종 형태인 mature miRNA의 정확한 위치 예측은 miRNA 예측의 필수적인 부분이다. 본 논문에서는, 진화적 최적화 예측 모델 중 하나인 유전 알고리즘을 이용하여 mature miRNA의 정확한 위치 예측을 수행한다. 제시된 방법은 이미 알려진 mature miRNA 위치를 positive example로 하고 임의로 생성한 위치를 negative example로 하여 서로의 linear scoring function 적합성 함수의 값 차이가 최대한으로 되도록 예측 모델을 진화시킨다. 유전 알고리즘을 이용한 진화적 최적화 모델로부터 mature miRNA 위치 예측에서 약 1.7nt 오차를 보여 기존의 방법 보다 개선된 성능을 보인다.

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Identification of Caenorhabditis elegans microRNA target using a neural network (신경망을 이용한 예쁜 꼬마 선충 microRNA target 예측)

  • Lee, Wha-Jin;Zhang, Byoung-Tak
    • Proceedings of the Korean Society for Bioinformatics Conference
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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.

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