ORIGINAL ARTICLE   

Journal of Neurosurgical Sciences 2022 April;66(2):125-32

DOI: 10.23736/S0390-5616.20.04773-6

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

Investigation of key miRNAs and their target genes involved in cell apoptosis during intervertebral disc degeneration development using bioinformatics methods

Haocong ZHANG ¹, Meng ZHANG ², Lingzhi MENG ¹, Mingming GUO ¹, Meihui PIAO ¹, Zijun HUANG ², Hailong YU ¹ ✉

¹ Department of Orthopaedics, The General Hospital of Northern Theater Command, Shenyang, China; ² The Second Clinical College of Graduate School, Dalian Medical University, Dalian, China

BACKGROUND: The aim of this study was to identify important miRNAs and their target genes involved in cell apoptosis in intervertebral disc degeneration (IDD) patients.
METHODS: The dataset, GSE63492, was obtained from the gene expression omnibus platform. After preprocessing, the differentially expressed miRNAs (DEMs) and their target genes were identified using the Limma package and miRWalk2.0 database, respectively. The clusterProfiler package in R was used to perform functional enrichment analysis of these target genes. Subsequently, protein-protein interaction (PPI) network and subnet clusters of the coregulated genes were conducted using the STRING database and MCODE, respectively. Further, the co-regulatory network of the key miRNAs and PPI networks were visualized using Cytoscape. Finally, cell apoptosis-related pathways and the genes enriched in these pathways were identified.
RESULTS: The genes targeted by the upregulated (hsa-miR-302c-5p, hsa-miR-631, hsa-let-7f-1-3p, hsa-miR-3675-3p, and hsa-miR-585-3p) and downregulated miRNAs (hsa-miR-185-5p, hsa-miR-486-5p, hsa-miR-4306, and hsa-miR-4674) were interrelated with cell apoptosis-related pathways. MAPK1 and MAPK3 were targeted by hsa-miR-185-5p, while GSK3B was targeted hsa-miR-4306, hsa-miR-486-5p, hsa-miR-185-5p, hsa-let-7f-1-3p, and hsa-miR-631. Besides, MAPK3 and VEGFA were regulated by hsa-miR-3675-3p and hsa-miR-631, respectively.
CONCLUSIONS: The expression of GSK3B may be coregulated by miR-4306, miR-185-5p, miR-486-5p, hsa-let-7f-1-3p, and miR-631 and may affect IDD development. Besides, miR-185-5p and miR-3675-3p may control nucleus pulposus (NP) cell apoptosis through the MAPK signaling pathway in IDD patients. VEGFA expression may be regulated by miR-631, and help maintain NP cell survival in IDD patients. Our findings may help guide further research into the role of miRNAs in IDD progression.

KEY WORDS: Intervertebral disc degeneration; Nucleus pulposus; Apoptosis; MicroRNAs