Structural effects of cross-kingdom miRNA on regulation of RNA function in cancer

跨界 miRNA 对癌症 RNA 功能调节的结构影响

• 批准号: 2445944
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2445944
• 关键词: Structural; effects; cross; kingdom; miRNA

MicroRNAs (miRNAs) are a class of short (17-25 nucleotides), non-coding RNA that regulate post-transcriptional silencing of target genes. A single miRNA can target multiple mRNAs and impact the expression of many genes. In general, miRNAs are key regulators of numerous biological processes such as development, stress response, growth and other physiological processes. In 2012, it was found that plant miRNAs are able to inhibit mammalian gene expression in liver through food intake; demonstrating the first case of cross-kingdom regulation. Countinuing this research path, in 2015, it was found that oral administered mixtures of tumour suppressor miRNAs reduced tumour burden in a mouse model of colon cancer. These observations demonstrate that plant miRNA is absorbed by the mammalian digestive system; therefore, target mammalian gene activity. Moreover, they suggest the hypothesis that engineered edible plant miRNAs with tumour repressor properties could be a novel approach for cancer treatment. This would provide an effective, non-toxic, chemo-preventitive treatment plan for humans.Recently, Shu and collaborators highlighted the potential computational approach to identify plant miRNA and mammalian mRNA interactions. A comperative analysis was applied focusing on inferring the likelihood of exogenous miRNA in human circulation. High-throughput sequencing technologies have made the computational approach potentially quicker and more cost-effective than standard laboratory methods. Using these technologies the knowledge gained about the miRNA universe rapidly increases. Several computational technologies have been developed to assess and predict miRNA:mRNA interactions such as miRanda, TargetScan, PITA and PicTar. Most algorithms use experimental knowledge to develop a specific scoring system such as miRNA:mRNA partial complementarity, seed region, target position and sequence convservation features. In 2013, Coronello and Benos developed a web tool for combinatorial miRNA target prediction called COMIR, which combines four scoring schemes (miRanda, PITA, TargetScan and mirSVF) to predict potential target genes. In 2016, the industrial partner MirNat developed MirCompare, a web application with the aim to identify plant and mammalian miRNA functional homologies as plant miRNA tend to have stringent selectivity for possible binding sites.In this project, the aim is to advance these computational approaches working together with the industrial partner on MirCompare and design a pipeline that detects miRNA sites eligible for mRNA binding.

microRNA（miRNAs）是一类短的（17-25个核苷酸）非编码RNA，其调节靶基因的转录后沉默。单个miRNA可以靶向多个mRNA并影响许多基因的表达。一般而言，miRNA是许多生物过程如发育、应激反应、生长和其他生理过程的关键调节因子。2012年，发现植物miRNAs能够通过食物摄入抑制哺乳动物肝脏中的基因表达;证明了第一例跨王国调控。继续这一研究路径，在2015年，人们发现口服肿瘤抑制剂miRNAs的混合物减少了结肠癌小鼠模型的肿瘤负担。这些观察结果表明，植物miRNA被哺乳动物消化系统吸收;因此，靶向哺乳动物基因活性。此外，他们提出了一种假设，即具有肿瘤抑制剂特性的工程化可食用植物miRNAs可能是癌症治疗的新方法。这将为人类提供一个有效的，无毒的，化学预防性的治疗计划。最近，Shu和合作者强调了潜在的计算方法来识别植物miRNA和哺乳动物mRNA的相互作用。应用比较分析，重点推断人体循环中外源性miRNA的可能性。高通量测序技术使得计算方法可能比标准实验室方法更快，更具成本效益。利用这些技术，人们对miRNA宇宙的了解迅速增加。已经开发了几种计算技术来评估和预测miRNA：mRNA相互作用，例如米兰达、TargetScan、PITA和PicTar。大多数算法使用实验知识来开发特定的评分系统，例如miRNA：mRNA部分互补性，种子区域，靶位置和序列一致性特征。2013年，Coronello和Benos开发了一种用于组合miRNA靶点预测的网络工具，称为COMIR，它结合了四种评分方案（米兰达，PITA，TargetScan和mirSVF）来预测潜在的靶基因。2016年，工业合作伙伴MirNat开发了MirCompare，这是一个网络应用程序，旨在识别植物和哺乳动物miRNA功能同源性，因为植物miRNA往往对可能的结合位点具有严格的选择性。在该项目中，目标是与MirCompare上的工业合作伙伴合作推进这些计算方法，并设计一个检测适合mRNA结合的miRNA位点的管道。