Xu Peng, Wu Qian, Yu Jian, Rao Yongsheng, Kou Zheng, Fang Gang, Shi Xiaolong, Liu Wenbin, Han Henry
Institute of Computational Science and Technology, Guangzhou University, Guangzhou, China.
School of Computer Science of Information Technology, Qiannan Normal University for Nationalities, Duyun, China.
Front Genet. 2020 Mar 31;11:278. doi: 10.3389/fgene.2020.00278. eCollection 2020.
MicroRNAs (miRNAs) are a class of important non-coding RNAs, which play important roles in tumorigenesis and development by targeting oncogenes or tumor suppressor genes. One miRNA can regulate multiple genes, and one gene can be regulated by multiple miRNAs. To promote the clinical application of miRNAs, two fundamental questions should be answered: what's the regulatory mechanism of a miRNA to a gene, and which miRNAs are important for a specific type of cancer. In this study, we propose a miRNA influence capturing (miRNAInf) to decipher regulation relations of miRNAs on target genes and identify critical miRNAs in cancers in a systematic approach. With the pair-wise miRNA/gene expression profiles data, we consider the assigning problem of a miRNA on target genes and determine the regulatory mechanisms by computing the Pearson correlation coefficient between the expression changes of a miRNA and that of its target gene. Furthermore, we compute the relative local influence strength of a miRNA on its target gene. Finally, integrate the local influence strength and target gene's importance to determine the critical miRNAs involved in specific cancer. Results on breast, liver and prostate cancers show that positive regulations are as common as negative regulations. The top-ranked miRNAs show great potential as therapeutic targets driving cancer to a normal state, and they are demonstrated to be closely related to cancers based on biological functional analysis, drug sensitivity/resistance analysis and survival analysis. This study will be helpful for the discovery of critical miRNAs and development of miRNAs-based clinical therapeutics.
微小RNA（miRNAs）是一类重要的非编码RNA，它们通过靶向癌基因或肿瘤抑制基因在肿瘤发生和发展过程中发挥重要作用。一个miRNA可以调控多个基因，而一个基因也可以被多个miRNA调控。为了促进miRNAs在临床上的应用，需要回答两个基本问题：miRNA对基因的调控机制是什么，以及哪些miRNA对特定类型的癌症至关重要。在本研究中，我们提出了一种微小RNA影响捕获方法（miRNAInf），以系统的方式解读miRNA对靶基因的调控关系，并识别癌症中的关键miRNA。利用成对的miRNA/基因表达谱数据，我们考虑miRNA对靶基因的分配问题，并通过计算miRNA与其靶基因表达变化之间的皮尔逊相关系数来确定调控机制。此外，我们计算了miRNA对其靶基因的相对局部影响强度。最后，综合局部影响强度和靶基因的重要性来确定参与特定癌症的关键miRNA。乳腺癌、肝癌和前列腺癌的研究结果表明，正向调控与负向调控一样常见。排名靠前的miRNA作为将癌症驱动至正常状态的治疗靶点具有巨大潜力，并且基于生物学功能分析、药物敏感性/抗性分析和生存分析表明它们与癌症密切相关。本研究将有助于发现关键miRNA以及开发基于miRNA的临床治疗方法。
