Identification of miRNA-TF Regulatory Pathways Related to Diseases from a Neuroendocrine-Immune Perspective

The neuroendocrine-immune (NEI) network is fundamental for maintaining body's homeostasis and health. While the roles of microRNAs (miRNAs) and transcription factors (TFs) in disease processes are well-established, their synergistic regulation within the NEI network has yet to be elucidated. In this study, we constructed a background NEI-related miRNA-TF regulatory network (NEI-miRTF-N) by integrating NEI signaling molecules (including miRNAs, genes, and TFs) and identifying miRNA-TF feed-forward loops. Our analysis reveals that the number of immune signaling molecules is the highest and suggests potential directions for signal transduction, primarily from the nervous system to both the endocrine and immune systems, as well as from the endocrine system to the immune system. Furthermore, disease-specific NEI-miRTF-Ns for depression, Alzheimer's disease (AD) and dilated cardiomyopathy (DCM) were constructed based on the known disease molecules and significantly differentially expressed (SDE) molecules. Additionally, we proposed a novel method using depth-first-search algorithm for identifying significantly dysregulated NEI-related miRNA-TF regulatory pathways (NEI-miRTF-Ps) and verified their reliability from multiple perspectives. Our study provides an effective approach for identifying disease-specific NEI-miRTF-Ps and offers new insights into the synergistic regulation of miRNAs and TFs within the NEI network. Our findings provide information for new therapeutic strategies targeting these regulatory pathways.