• 제목/요약/키워드: microRNA-34

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

  • 남진우;장병탁
    • 한국정보과학회:학술대회논문집
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    • 한국정보과학회 2006년도 한국컴퓨터종합학술대회 논문집 Vol.33 No.1 (A)
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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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태반유래 줄기세포와 골수유래 줄기세포에서의 마이크로RNA 발현비교 (Comparison of MicroRNA Expression in Placenta-derived Mesenchymal Stem Cells and Bone Marrow-derived Stem Cells)

  • 김수환
    • 생명과학회지
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    • 제24권11호
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    • pp.1238-1243
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    • 2014
  • 중간엽줄기세포(mesenchymal stem cell, MSC)은 세포치료로 각광받아 널리 사용되고 있다. 이들은 줄기세포의 분화성을 이용하여 많은 만성질환에 연관되어 치료제로 사용되고 있다. 줄기세포는 다른 화학적 치료법에 비해 많은 장점을 가지고 있다. 왜냐하면 줄기세포치료는 자기자신, 혹은 동종의 세포를 이용한 치료이기 때문에 화학 치료에 비해 부작용이나 치료의 위험성이 덜하다. 그리고 마이크로RNA또한 최근 기 존재와 기능이 밝혀져서 연구되고 있는데 특히 항암, 세포생장촉진 등의 기능을 이용해 항암, 만성질환 치료에 접목되어 치료제로의 역할이 기대된다. 마이크로RNA는 대부분의 대사과정이나 항상성조절에 관여되어있다. 따라서 마이크로RNA가 저 발현 혹은 과 발현하게 되면 만성질환으로 이어지게 된다. 하지만 줄기세포와 마이크로RNA의 상호간 보조효과는 잘 연구되어 있지 않다. 따라서 이들 간의 상관관계를 확인하기 위하여 태반유래 줄기세포(PDSC)와 골수줄기세포(BM-MSC), 대조군으로 섬유아세포(Fibroblast, WI-38)을 사용하여 이들이 발현하는 마이크로RNA 발현을 확인해 보았다. 각각의 MSC 세포주에 대하여 특정 마이크로RNA의 발현량을 확인해 보았다. 결과 PDSC의 경우엔 마이크로RNA-34a의 발현이 높았고 BM-MSC의 경우에는 마이크로RNA-27a, 33a, 33b, 211의 발현이 높은 것을 확인할 수 있었다. 따라서 우리는 각각의 MSC세포주와 그들이 발현하는 기능성 마이크로RNA을 연관지어 효과적인 세포치료에 활용될 수 있을 것을 기대한다.

Down-regulation of miR-34a Expression in Cervical Intraepithelial Neoplasia with Human Papillomavirus Infection and Its Relationship with p53 Expression

  • Lee, Kyung Eun
    • 대한의생명과학회지
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    • 제19권4호
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    • pp.348-352
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    • 2013
  • microRNAs (miRNAs) play pivotal roles in controlling cell proliferation and differentiation. miRNA expression in human is becoming recognized as a new molecular mechanism of carcinogenesis. microRNA-34a (miR-34a), a member of the p53 network, was found to be regulated in multiple types of tumor. The purpose of this study was to define roles of miR-34a expression in cervical intraepithelial neoplasia with human papillomavirus infection, and its relationship with p53 protein expression. This study was performed to analyze expression of miR-34a by using qRT-PCR, and to evaluate p53 protein expression by using immunohistochemistry in 40 cases. Down-regulation of miR-34a expression was detected in 27 (67.5%) out of 40 cases and Immunoreactivity for p53 was found in 17 (42.5%) out of 40 cases. Nineteen (82.6%) of the 23 cases with a negative p53 expression showed a down-regulation miR-34a expression, there was a significant associations between miR-34a and p53 protein expression (P=0.04). These results suggest that miRNA-34a expression tend to be reduced depending on the advanced histologic grade, and down-regulation of miR-34a expression might be associated with inactivation of p53 protein expression by human papillomavirus infection.

족삼리 양릉천 전침 자극 후 흰쥐 통증 모델에서 microRNA의 차등 발현 (Differential Expression of microRNAs Following Electroacupuncture Applied to ST36 and GB34 in Rat Models of Chronic Pain)

  • 김소희;비슈누몰라칼라 신드후리;구성태
    • Korean Journal of Acupuncture
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    • 제39권4호
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    • pp.132-141
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    • 2022
  • Objectives : Some acupoints are commonly utilized to treat a variety of diseases. The acupoints appear to have a wide range of effects caused by several mechanisms. The purpose of this study is to investigate into the potential role of microRNAs (miRNAs) in the multipotent effects of individual acupoint stimulation. Methods : We examined the miRNA expressions in the dorsal root ganglia (DRG) of neuropathic or inflammatory pain rats following ST36 and GB34 electroacupuncture (EA) stimulation. Neuropathic pain was induced by L5 spinal nerve ligation. Inflammatory pain was induced by knee joint injection of Complete Freund's adjuvant (CFA). EA was given under gaseous anesthesia with the same parameters (1mA, 2Hz, 30 min) in 5 consecutive days. Pain behaviors and miRNA expressions were analyzed. Results : In rats with neuropathic and inflammatory pain, EA treatments significantly enhanced the paw withdrawal threshold and weight-bearing force. After nerve injury, 36 miRNAs were upregulated in the DRG of neuropathic rats, while EA downregulated 10 of them. Furthermore, 14 miRNAs were downregulated following nerve damage, while one was increased by EA. 15 miRNAs were increased in the DRG of inflammatory rats following CFA injection, while 5 were downregulated by EA. Furthermore, 17 miRNAs were downregulated following CFA injection, while 7 were increased by EA. The miRNAs rno-miR-335, rno-miR-381-5p, rno-miR-1306-3p, and rno-miR-1839-3p were regulated by EA in both models. Conclusions : In two pain models, EA applied to ST36 and GB34 regulated miRNA expression differently. There appeared to be both acupoint-specific and non-specific miRNAs, and miRNA regulation of differential protein expression may modulate a variety of EA mechanisms.

건칠(乾漆)을 이용한 K562 만성 골수성 백혈병 세포주에서의 MicroRNA 발현 규명 (MicroRNA Expression in Leukemia Cell Line(K562 cell) Using Rhus Verniciflua Stokes)

  • 최현숙
    • 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.

Down Regulation of miR-34a and miR-143 May Indirectly Inhibit p53 in Oral Squamous Cell Carcinoma: a Pilot Study

  • Manikandan, Mayakannan;Rao, Arunagiri Kuha Deva Magendhra;Arunkumar, Ganesan;Rajkumar, Kottayasamy Seenivasagam;Rajaraman, Ramamurthy;Munirajan, Arasambattu Kannan
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권17호
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    • pp.7619-7625
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    • 2015
  • Background: Aberrant microRNA expression has been associated with the pathogenesis of a variety of human malignancies including oral squamous cell carcinoma (SCC). In this study, we examined primary oral SCCs for the expression of 6 candidate miRNAs, of which five (miR-34a, miR-143, miR-373, miR-380-5p, and miR-504) regulate the tumor suppressor TP53 and one (miR-99a) is involved in AKT/mTOR signaling. Materials and Methods: Tumor tissues (punch biopsies) were collected from 52 oral cancer patients and as a control, 8 independent adjacent normal tissue samples were also obtained. After RNA isolation, we assessed the mature miRNA levels of the 6 selected candidates against RNU44 and RNU48 as endogenous controls, using specific TaqMan miRNA assays. Results: miR-34a, miR-99a, miR-143 and miR-380-5p were significantly down-regulated in tumors compared to controls. Moreover, high levels of miR-34a were associated with alcohol consumption while those of miR-99a and miR-143 were associated with advanced tumor size. No significant difference was observed in the levels of miR-504 between the tumors and controls whereas miR-373 was below the detection level in all but two tumor samples. Conclusions: Low levels of miR-380-5p and miR-504 that directly target the 3'UTR of TP53 suggest that p53 may not be repressed by these two miRNAs in OSCC. On the other hand, low levels of miR-34a or miR-143 may relieve MDM4 and SIRT1 or MDM2 respectively, which will sequester p53 indicating an indirect mode of p53 suppression in oral tumors.

DETERMINATION OF PURINE AND PYRIMIDINE BASES IN RUMEN MICRO-ORGANISMS BY REVERSED PHASE HPLC AFTER HYDROLYTIC DIGESTION UNDER PRESSURE

  • Han, Y.K.;Landis, J.
    • Asian-Australasian Journal of Animal Sciences
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    • 제4권2호
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    • pp.161-164
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    • 1991
  • A rapid and accurate method is described for the determination of nucleo-bases in rumen micro-organisms. A procedure to satisfactorily hydrolyse the micro-organisms involving reaction with a mixture of readily volatile organic acids (acetic and formic acids) under high pressure, is proposed, and optimal conditions for an analytical procedure with reversed phase HPLC is described. The following nucleobases contents (mmol/kg DM) of rumen micro-organisms were found: Adenine (Ade), 82.62; Guanine (Gua), 61.34; Cytosine (Cyt), 84.61; Thymine (Thy), 35.74; Uracil (Ura), 68.62; Hypoxanthine (Hxn), 13.06; Xanthine (Xn), 8.35. Total purine-N content (g/kg N) of rumen micro-organisms were 99.60. The nucleic acid N content (g/kg N) of microbial isolates were: RNA-N, 109.9; DNA-N, 50.9.

Analysis of microRNA expression profiles during the cell cycle in synchronized HeLa cells

  • Zhou, Jue-Yu;Ma, Wen-Li;Liang, Shuang;Zeng, Ye;Shi, Rong;Yu, Hai-Lang;Xiao, Wei-Wei;Zheng, Wen-Ling
    • BMB Reports
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    • 제42권9호
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    • pp.593-598
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    • 2009
  • Cell cycle progression is regulated by both transcriptional and post-transcriptional mechanisms. MicroRNAs (miRNAs) emerge as a new class of small non-coding RNA regulators of cell cycle as recent evidence suggests. It is hypothesized that expression of specific miRNAs oscillates orderly along with cell cycle progression. However, the oscillated expression patterns of many candidate miRNAs have yet to be determined. Here, we describe miRNA expression profiling in double-thymidine synchronized HeLa cells as cell cycle progresses. Twenty-five differentially expressed miRNAs were classified into five groups based on their cell cycle-dependent expression patterns. The cyclic expression of six miRNAs (miR-221, let-7a, miR-21, miR-34a, miR-24, miR-376b) was validated by real-time quantitative RT-PCR (qRT-PCR). These results suggest that specific miRNAs, along with other key factors are required for maintaining and regulating proper cell cycle progression. The study deepens our understanding on cell cycle regulation.

Antiviral Efficacy of a Short PNA Targeting microRNA-122 Using Galactosylated Cationic Liposome as a Carrier for the Delivery of the PNA-DNA Hybrid to Hepatocytes

  • Kim, Hyoseon;Lee, Kwang Hyun;Kim, Kyung Bo;Park, Yong Serk;Kim, Keun-Sik;Kim, Dong-Eun
    • Bulletin of the Korean Chemical Society
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    • 제34권3호
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    • pp.735-742
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    • 2013
  • Peptide nucleic acids (PNAs) that bind to complementary nucleic acid sequences with extraordinarily high affinity and sequence specificity can be used as antisense oligonucleotides against microRNAs, namely antagomir PNAs. However, methods for efficient cellular delivery must be developed for effective use of PNAs as therapeutic agents. Here, we demonstrate that antagomir PNAs can be delivered to hepatic cells by complementary DNA oligonucleotide and cationic liposomes containing galactosylated ceramide and a novel cationic lipid, DMKE (O,O'-dimyristyl-N-lysyl glutamate), through glycoprotein-mediated endocytosis. An antagomir PNA was designed to target miR-122, which is required for translation of the hepatitis C virus (HCV) genome in hepatocytes, and was hybridized to a DNA oligonucleotide for complexation with cationic liposome. The PNA-DNA hybrid molecules were efficiently internalized into hepatic cells by complexing with the galactosylated cationic liposome in vitro. Galactosylation of liposome significantly enhanced both lipoplex cell binding and PNA delivery to the hepatic cells. After 4-h incubation with galactosylated lipoplexes, PNAs were efficiently delivered into hepatic cells and HCV genome translation was suppressed more than 70% through sequestration of miR-122 in cytoplasm. PNAs were readily released from the PNA-DNA hybrid in the low pH environment of the endosome. The present study indicates that transfection of PNA-DNA hybrid molecules using galactosylated cationic liposomes can be used as an efficient non-viral carrier for antagomir PNAs targeted to hepatocytes.

자궁내막암종에서 miR-23b와 miR-203 발현 비교 (Comparison of the miR-23b and miR-203 Expressions in Endometrial Cancer)

  • 이경은
    • 대한임상검사과학회지
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    • 제49권4호
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    • pp.455-459
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    • 2017
  • MicroRNA는 작은 비암호화 RNA로서 유전자 발현을 조절한다. 다양한 인체 종양에서 특이 miRNA 발현의 변화가 보고되면서 종양 발생에 중요한 역할을 수행하는 것으로 알려졌다. 최근에는 자궁내막암종을 포함한 다양한 암종에서 여러 miRNA의 비정상적인 발현이 보고되었으나, miR-23b와 miR-203 발현에 대한 연구 결과는 아직 국내에 보고되지 않았다. 따라서 본 연구에서는 자궁내막암종에서 miR-23b와 miR-203의 발현을 비교하고 상호 연관성을 분석하고자 하였다. 인체 자궁내막암종으로 진단된 파라핀 블록 42건을 대상으로 quantitative real-time PCR을 이용하여 miRNA 발현 수치를 분석하였다. miR-23b 발현 수치는 $2.70{\pm}4.45$로 miR-203의 발현 수치 $-2.34{\pm}4.08$ 보다 높게 나타났다. 또한 miR-23b는 총 42건 중 30건(71.4%)에서 양의 발현이 나타났고, miR-203은 총 42건 중 29건(69.0%)에서 음의 발현이 나타났으며, 이는 통계학적으로 유의한 차이를 나타냈다(p=0.0005). 따라서 본 연구에서는 miR-23b와 miR-203 발현은 자궁내막암종 발생에 연관이 있을 것으로 추정되며, 향후 miR-23b 와 miR-203 발현과 조직특이 단백 발현과의 상호 연관성에 대한 연구가 더 필요할 것으로 사료된다.