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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Systematical Identification of Breast Cancer-Related Circular RNA Modules for Deciphering circRNA Functions Based on the Non-Negative Matrix Factorization Algorithm
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Systematical Identification of Breast Cancer-Related Circular RNA Modules for Deciphering circRNA Functions Based on the Non-Negative Matrix Factorization Algorithm

机译：基于非负矩阵分解算法的用于破译circRNA功能的乳腺癌相关环状RNA模块的系统鉴定

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Circular RNA (circRNA), a kind of special endogenous RNA, has been shown to be implicated in crucial biological processes of multiple cancers as a gene regulator. However, the functional roles of circRNAs in breast cancer (BC) remain to be poorly explored, and relatively incomplete knowledge of circRNAs handles the identification and prediction of BC-related circRNAs. Towards this end, we developed a systematic approach to identify circRNA modules in the BC context through integrating circRNA, mRNA, miRNA, and pathway data based on a non-negative matrix factorization (NMF) algorithm. Thirteen circRNA modules were uncovered by our approach, containing 4164 nodes (80 circRNAs, 2703 genes, 63 miRNAs and 1318 pathways) and 67,959 edges in total. GO (Gene Ontology) function screening identified nine circRNA functional modules with 44 circRNAs. Within them, 31 circRNAs in eight modules having direct relationships with known BC-related genes, miRNAs or disease-related pathways were selected as BC candidate circRNAs. Functional enrichment results showed that they were closely related with BC-associated pathways, such as ‘KEGG (Kyoto Encyclopedia of Genes and Genomes) PATHWAYS IN CANCER’, ‘REACTOME IMMUNE SYSTEM’ and ‘KEGG MAPK SIGNALING PATHWAY’, ‘KEGG P53 SIGNALING PATHWAY’ or ‘KEGG WNT SIGNALING PATHWAY’, and could sever as potential circRNA biomarkers in BC. Comparison results showed that our approach could identify more BC-related functional circRNA modules in performance. In summary, we proposed a novel systematic approach dependent on the known disease information of mRNA, miRNA and pathway to identify BC-related circRNA modules, which could help identify BC-related circRNAs and benefits treatment and prognosis for BC patients.
机译：环状RNA（circRNA）是一种特殊的内源RNA，已被证明与多种癌症的重要生物学过程有关，作为基因调节剂。但是，circRNA在乳腺癌（BC）中的功能作用尚待探讨，并且对circRNA的相对不完整的知识可用于BC相关circRNA的鉴定和预测。为此，我们开发了一种系统方法，通过基于非负矩阵分解（NMF）算法整合circRNA，mRNA，miRNA和途径数据，在BC环境中识别circRNA模块。我们的方法发现了13个circRNA模块，总共包含4164个节点（80个circRNA，2703个基因，63个miRNA和1318个途径）和67,959条边。 GO（基因本体论）功能筛选确定了具有44个circRNA的9个circRNA功能模块。在其中，与已知的BC相关基因，miRNA或疾病相关途径具有直接关系的八个模块中的31个circRNA被选作BC候选circRNA。功能富集结果表明，它们与BC相关途径密切相关，例如“ KEGG（癌症基因和基因组京都百科全书）途径”，“反应免疫系统”和“ KEGG MAPK信号通路”，“ KEGG P53信号通路”或“ KEGG WNT SIGNALING PATHWAY”，并且可能被切断为BC中潜在的circRNA生物标记。比较结果表明，我们的方法可以鉴定出更多与BC相关的功能circRNA模块。总而言之，我们提出了一种新颖的系统方法，该方法依赖于已知的mRNA，miRNA和途径的疾病信息来鉴定BC相关circRNA模块，这可以帮助鉴定BC相关circRNA，并有益于BC患者的治疗和预后。

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