Research Paper Volume 14, Issue 8 pp 3569—3596

Effective biomarkers and therapeutic targets of nerve-immunity interaction in the treatment of depression: an integrated investigation of the miRNA-mRNA regulatory networks

Zixuan Wu1, *, , Zhixiang Cai1, *, , Hongshuo Shi2, *, , Xuyan Huang1, , Minjie Cai1,4, , Kai Yuan5, , Peidong Huang5, , Guoqi Shi1, , Tao Yan1,6, , Zhichao Li3, ,

  • 1 Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
  • 2 Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
  • 3 The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
  • 4 Shantou Health School, Shantou 515061, Guangdong Province, China
  • 5 Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
  • 6 Department of Cardiovascular Surgery, General Hospital of Southern Theater Command, PLA 510010, Guangdong Province, China
* Equal contribution and co-first authors

Received: December 28, 2021       Accepted: April 11, 2022       Published: April 25, 2022
How to Cite

Copyright: © 2022 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Major depressive disorder (MDD) is an emotional condition that interferes with sufferers’ work and daily life. Numerous studies have found that miRNAs play a significant role in the development of MDD and can be utilized as a biomarker for its diagnosis and therapy. However, there have been few studies on nerve-immunity interaction treatment for the brains of MMD patients. Methods: The work is performed on microarray data. We analyzed the differences of miRNAs (GSE58105, GSE81152, GSE152267, and GSE182194) and mRNA (GSE19738, GSE32280, GSE44593, GSE53987, and GSE98793) in MDD and healthy samples from GEO datasets. FunRich was used to predict the transcription factors and target genes of the miRNAs, and TF and GO enrichment analyses were performed. Then, by comparing the differential expression of the anticipated target genes and five mRNAs, intersecting mRNAs were discovered. The intersecting genes were submitted to GO and KEGG analyses to determine their functions. These intersecting potential genes and pathways that linked to MDD in neurological and immunological aspects have been identified for future investigation. Results: We discovered five hub genes: KCND2, MYT1L, GJA1, CHL1, and SNAP25, which were all up-regulated genes. However, in MMD, the equivalent miRNAs, hsa-miR-206 and hsa-miR-338-3p, were both down-regulated. These miRNAs can activate or inhibit the T cell receptor signal pathway, JAK-STAT and other signal pathways, govern immune-inflammatory response, neuronal remodeling, and mediate the onset and development of MMD Conclusions: The results of a thorough bioinformatics investigation of miRNAs and mRNAs in MDD showed that miR-338-3P and miR-206 might be effective biomarkers and possible therapeutic targets for the treatment of MDD via nerve-immunity interaction.


MDD: Major depressive disorder; GO: Gene Ontology; TCM: Traditional Chinese medicine; MF: Molecular functions; KEGG: Kyoto Encyclopedia of Genes and Genomes; TF: Transcription Factor; GEO: Gene Expression Omnibus; MiRNAs: MicroRNAs MiRNAs; BP: Biological processes; CC: Cellular components; DEGs: Differentially Expressed Genes.