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

MicroRNAs （miRNAs）是一类短的（17-25个核苷酸）非编码RNA，可调节靶基因的转录后沉默。单个miRNA可以靶向多个mrna，影响许多基因的表达。一般来说，mirna是许多生物过程的关键调节剂，如发育、应激反应、生长和其他生理过程。2012年，研究发现植物mirna能够通过食物摄入抑制哺乳动物肝脏中的基因表达；展示了跨王国监管的第一个案例。继续这一研究路径，在2015年，研究人员发现口服肿瘤抑制miRNAs混合物可以降低结肠癌小鼠模型的肿瘤负荷。这些观察结果表明，植物miRNA可被哺乳动物消化系统吸收；因此，针对哺乳动物的基因活性。此外，他们还提出了一种假设，即具有肿瘤抑制因子特性的可食用植物mirna可能是一种治疗癌症的新方法。这将为人类提供一种有效、无毒、化学预防的治疗方案。最近，Shu和合作者强调了识别植物miRNA和哺乳动物mRNA相互作用的潜在计算方法。应用比较分析，重点推断外源性miRNA在人体循环中的可能性。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，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的相互作用，如miRanda、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，如miRNA:mRNA部分互补、种子区域、目标位置和序列保守特征。2013年，Coronello和Benos开发了一种用于组合miRNA靶标预测的网络工具COMIR，该工具结合了四种评分方案（miRanda， PITA， TargetScan和mirSVF）来预测潜在的靶基因。2016年，行业合作伙伴MirNat开发了MirCompare，这是一个web应用程序，旨在识别植物和哺乳动物miRNA的功能同源性，因为植物miRNA对可能的结合位点具有严格的选择性。在这个项目中，目标是与MirCompare的工业合作伙伴一起推进这些计算方法，并设计一个检测符合mRNA结合条件的miRNA位点的管道。

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.