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. 2021 Jan 28;11:2416. doi: 10.1038/s41598-021-81962-6

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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3-node, 4-node and 5 node motifs. (A) 15 different types of 3-node regulatory motifs. (B) 29 different types of 4-node regulatory motifs. (C) 39 screened different types of 5-node regulatory motifs. The motifs are composed of miRNAs, TFs, and target genes and their Z-scores and p value s are presented. Orange triangles represent miRNAs, green rounds represent TFs and purple squares represent genes. An arrow ending in a circle represents the regulatory relationship, while, an arrow ending in a “T” represents the repression relationship. Six types of relationships involved in these motifs: miRNA–gene (miRNA represses gene expression); miRNA–TF (miRNA represses TF gene expression); TF–miRNA (TF regulates miRNA expression); TF–gene (TF regulates gene expression); gene–gene (gene and gene interaction); and miRNA–miRNA (miRNA and miRNA interaction). Motifs surrounded by red squares (3-node, 4-node and 5-node composite feed-forward loop) as significant motifs were merged to form 3-node, 4-node and 5-node regulatory sub-networks, respectively. TF: transcription factor; FFL: feed-forward loop.