慢性髓系白血病中潜在的跨界植物MicroRNA调控的计算机研究

Q4 Pharmacology, Toxicology and Pharmaceutics Current Pharmacogenomics and Personalized Medicine Pub Date : 2020-10-28 DOI:10.2174/1875692118666200106113610
M. H. Elias, Noraziah Nordin, N. A. Hamid
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引用次数: 1

摘要

慢性髓性白血病(CML)与bcrabl1基因相关,该基因在CML的发病机制中起核心作用。因此,抑制BCR-ABL1的表达在CML的治疗中至关重要。众所周知,MicroRNA是一种基因表达调节因子,因此是CML分子靶向治疗的良好候选者。本研究旨在鉴定可食用植物中靶向BCR-ABL1 3 ' untranslingregion (3'UTR)的microrna。在此计算机分析中,BCR-ABL1的3'UTR序列从Ensembl Genome Browser中获得。使用psrnatartanalysis Server和MicroRNA TargetPrediction (miRTar) Server来鉴定与BCR-ABL1 3'UTR结合符合的mirna。MiRBase数据库用于验证表达miRNAs的植物种类。使用RNA old web server和RNA COMPOSER分别进行二级和三级结构预测。芯片分析显示,cpa-miR8154、ci - mir3952、gma-miR4414-5p、mda - mir482c、osa-miR1858a和osa-miR1858b对BCR-ABL1的3'UTR区具有强分子相互作用。然而,只有cpa-miR-8154、osa-miR-1858a和osa-miR-1858b表现出良好的靶点可达性。据预测,这些microrna转录后抑制bcrabl1基因,因此可能成为CML的潜在分子靶向治疗方法。然而,需要进行进一步的体外、体内和功能分析研究,以确定这些mirna能否成为CML靶向治疗的基础。
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In Silico Study of Potential Cross-Kingdom Plant MicroRNA Based Regulation in Chronic Myeloid Leukemia
Chronic Myeloid Leukaemia (CML) is associated with the BCRABL1 gene, which plays a central role in the pathogenesis of CML. Thus, it is crucial to suppress the expression of BCR-ABL1 in the treatment of CML. MicroRNA is known to be a gene expression regulator and is thus a good candidate for molecularly targeted therapy for CML. This study aims to identify the microRNAs from edible plants targeting the 3’ Untranslated Region (3’UTR) of BCR-ABL1. In this in silico analysis, the sequence of 3’UTR of BCR-ABL1 was obtained from Ensembl Genome Browser. PsRNATarget Analysis Server and MicroRNA Target Prediction (miRTar) Server were used to identify miRNAs that have binding conformity with 3’UTR of BCR-ABL1. The MiRBase database was used to validate the species of plants expressing the miRNAs. The RNAfold web server and RNA COMPOSER were used for secondary and tertiary structure prediction, respectively. In silico analyses revealed that cpa-miR8154, csi-miR3952, gma-miR4414-5p, mdm-miR482c, osa-miR1858a and osa-miR1858b show binding conformity with strong molecular interaction towards 3’UTR region of BCR-ABL1. However, only cpa-miR- 8154, osa-miR-1858a and osa-miR-1858b showed good target site accessibility. It is predicted that these microRNAs post-transcriptionally inhibit the BCRABL1 gene and thus could be a potential molecular targeted therapy for CML. However, further studies involving in vitro, in vivo and functional analyses need to be carried out to determine the ability of these miRNAs to form the basis for targeted therapy for CML.
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来源期刊
Current Pharmacogenomics and Personalized Medicine
Current Pharmacogenomics and Personalized Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
0.40
自引率
0.00%
发文量
11
期刊介绍: Current Pharmacogenomics and Personalized Medicine (Formerly ‘Current Pharmacogenomics’) Current Pharmacogenomics and Personalized Medicine (CPPM) is an international peer reviewed biomedical journal that publishes expert reviews, and state of the art analyses on all aspects of pharmacogenomics and personalized medicine under a single cover. The CPPM addresses the complex transdisciplinary challenges and promises emerging from the fusion of knowledge domains in therapeutics and diagnostics (i.e., theragnostics). The journal bears in mind the increasingly globalized nature of health research and services.
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