Institute of computational science and technology, Guangzhou University, Guangzhou, 510006, Guangdong, China.
School of computer science of information technology, Qiannan Normal University for Nationalities, Duyun, 558000, Guizhou, China.
BMC Bioinformatics. 2020 Sep 7;21(1):396. doi: 10.1186/s12859-020-03732-x.
MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically.
In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anti-cancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group.
In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers.
MicroRNAs 是一类重要的小非编码 RNA，据报道通过靶向少数基因参与肿瘤发生和发展过程。现有研究表明，细胞增殖和凋亡之间的失衡与癌症的发生和发展密切相关。然而，miRNAs 对这种失衡的影响尚未被系统地研究。
在这项研究中，我们首先构建了细胞命运 miRNA-基因调控网络。然后，我们提出了一种基于最短路径计算 miRNAs 对细胞命运基因全局影响的系统方法。乳腺癌和肝癌数据集的结果表明，大多数细胞命运基因受到差异表达 miRNAs 的干扰。在人类 MicroRNA 疾病数据库 (HMDD) 中验证的 top 识别 miRNAs 大多与乳腺癌和肝癌相关。功能分析表明，前 20 个 miRNAs 调节多个细胞命运相关的功能模块，并基于其功能相似性紧密相互作用。此外，其中超过一半的 miRNA 可以促进对某些抗癌药物的敏感性或诱导耐药性。此外，生存分析表明，排名靠前的 miRNAs 与乳腺癌和肝癌组的总生存时间显著相关。
总之，这项研究有助于系统地研究 miRNAs 对增殖和凋亡的重要作用，从而揭示肿瘤发生过程中的关键 miRNAs。此外，这项研究的结果将有助于基于 miRNAs 的癌症临床治疗的发展。
