Zhang Junpeng, Le Thuc D, Liu Lin, Li Jiuyong
School of Engineering, Dali University, Dali, Yunnan, 671003, People's Republic of China.
School of Information Technology and Mathematical Sciences, University of South Australia, Mawson Lakes, SA, 5095, Australia.
BMC Bioinformatics. 2017 Mar 14;18(Suppl 3):44. doi: 10.1186/s12859-017-1467-5.
MicroRNA (miRNA) sponges with multiple tandem miRNA binding sequences can sequester miRNAs from their endogenous target mRNAs. Therefore, miRNA sponge acting as a decoy is extremely important for long-term loss-of-function studies both in vivo and in silico. Recently, a growing number of in silico methods have been used as an effective technique to generate hypotheses for in vivo methods for studying the biological functions and regulatory mechanisms of miRNA sponges. However, most existing in silico methods only focus on studying miRNA sponge interactions or networks in cancer, the module-level properties of miRNA sponges in cancer is still largely unknown.
We propose a novel in silico method, called miRSM (miRNA Sponge Module) to infer miRNA sponge modules in breast cancer. We apply miRSM to the breast invasive carcinoma (BRCA) dataset provided by The Cancer Genome Altas (TCGA), and make functional validation of the computational results. We discover that most miRNA sponge interactions are module-conserved across two modules, and a minority of miRNA sponge interactions are module-specific, existing only in a single module. Through functional annotation and differential expression analysis, we also find that the modules discovered using miRSM are functional miRNA sponge modules associated with BRCA. Moreover, the module-specific miRNA sponge interactions among miRNA sponge modules may be involved in the progression and development of BRCA. Our experimental results show that miRSM is comparable to the benchmark methods in recovering experimentally confirmed miRNA sponge interactions, and miRSM outperforms the benchmark methods in identifying interactions that are related to breast cancer.
Altogether, the functional validation results demonstrate that miRSM is a promising method to identify miRNA sponge modules and interactions, and may provide new insights for understanding the roles of miRNA sponges in cancer progression and development.
具有多个串联微小RNA（miRNA）结合序列的miRNA海绵体可以从其内源性靶mRNA中隔离miRNA。因此，miRNA海绵体作为一种诱饵对于体内和计算机模拟中的长期功能丧失研究极为重要。最近，越来越多的计算机模拟方法已被用作一种有效技术，为研究miRNA海绵体的生物学功能和调控机制的体内方法生成假设。然而，大多数现有的计算机模拟方法仅专注于研究癌症中的miRNA海绵体相互作用或网络，癌症中miRNA海绵体的模块水平特性在很大程度上仍然未知。
我们提出了一种名为miRSM（miRNA海绵体模块）的新型计算机模拟方法，用于推断乳腺癌中的miRNA海绵体模块。我们将miRSM应用于癌症基因组图谱（TCGA）提供的乳腺浸润性癌（BRCA）数据集，并对计算结果进行功能验证。我们发现大多数miRNA海绵体相互作用在两个模块中是模块保守的，少数miRNA海绵体相互作用是模块特异性的，仅存在于单个模块中。通过功能注释和差异表达分析，我们还发现使用miRSM发现的模块是与BRCA相关的功能性miRNA海绵体模块。此外，miRNA海绵体模块之间的模块特异性miRNA海绵体相互作用可能参与BRCA的进展和发展。我们的实验结果表明，miRSM在恢复实验证实的miRNA海绵体相互作用方面与基准方法相当，并且在识别与乳腺癌相关的相互作用方面优于基准方法。
总之，功能验证结果表明，miRSM是一种有前途的方法，可用于识别miRNA海绵体模块和相互作用，并可能为理解miRNA海绵体在癌症进展和发展中的作用提供新的见解。
