Background <p>Intervertebral disc degeneration (IDD), characterized by multifaceted pathological mechanisms, presents substantial therapeutic challenges. Globally, over 50% of individuals experience IDD-related low back pain (LBP), a debilitating condition associated with high recurrence rates and profound socioeconomic burdens. Current clinical strategies demonstrate limited efficacy in halting IDD progression, underscoring the critical need for targeted therapies.</p> Methods <p>We analyzed the gene expression data of IDD mRNA and miRNA in the GEO database. Subsequently, the mRNA was screened for differentially expressed genes (DEGs) using R language. Immediately after that, we conducted a screening analysis of DEGs on miRNAs, and then used Venn diagrams to obtain hub genes by taking the intersection of DEGs. Then, the function of the hub genes is enriched through miRDB. Then, the downstream target genes of miRNA hub genes are predicted through miRDB to construct the possible miRNA–mRNA regulatory network. Finally, we collected clinical nucleus pulposus (NP) tissues and constructed the degeneration models of nucleus pulposus cells (NPCs) and IDD in rats to verify the expression of mRNA DEGs and miRNA hub genes.</p> Results <p>We obtained a total of 29 differentially expressed genes from the GSE34095 and GSE70362 mRNA gene data sets, such as ERBB2 and POSTN. Five hub genes (hsa-miR-4741, hsa-miR-5100, hsa-miR-4306, hsa-miR-3158-5p, and hsa-miR-508-5p) were obtained from GSE63492 and GSE116726. It is functionally related to cell death, differentiation, transmembrane transport and tumorigenesis. Finally, we identified the following miRNA–mRNA regulatory networks: hsa-miR-508-5p-DRP2, hsa-miR-3158-ERBB2, hsa-miR-4306-POSTN and hsa-miR-5100-CAPRIN1. Subsequently, we verified our above findings using clinical IDD samples, senescent nucleus pulposus cell models, and IDD rat models.</p> Conclusions <p>These findings offer new insights into the occurrence and development of IDD and provide certain reference value for the subsequent diagnosis and treatment of IDD.</p>

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Screening and identification of differentially expressed miRNA and mRNA for intervertebral disc degeneration on bioinformatics

  • Jing Yan,
  • Yi Gao,
  • Rui Chen,
  • Shuo Miao,
  • Yuting Gong,
  • Yuning Zhu,
  • Quan Zhou

摘要

Background

Intervertebral disc degeneration (IDD), characterized by multifaceted pathological mechanisms, presents substantial therapeutic challenges. Globally, over 50% of individuals experience IDD-related low back pain (LBP), a debilitating condition associated with high recurrence rates and profound socioeconomic burdens. Current clinical strategies demonstrate limited efficacy in halting IDD progression, underscoring the critical need for targeted therapies.

Methods

We analyzed the gene expression data of IDD mRNA and miRNA in the GEO database. Subsequently, the mRNA was screened for differentially expressed genes (DEGs) using R language. Immediately after that, we conducted a screening analysis of DEGs on miRNAs, and then used Venn diagrams to obtain hub genes by taking the intersection of DEGs. Then, the function of the hub genes is enriched through miRDB. Then, the downstream target genes of miRNA hub genes are predicted through miRDB to construct the possible miRNA–mRNA regulatory network. Finally, we collected clinical nucleus pulposus (NP) tissues and constructed the degeneration models of nucleus pulposus cells (NPCs) and IDD in rats to verify the expression of mRNA DEGs and miRNA hub genes.

Results

We obtained a total of 29 differentially expressed genes from the GSE34095 and GSE70362 mRNA gene data sets, such as ERBB2 and POSTN. Five hub genes (hsa-miR-4741, hsa-miR-5100, hsa-miR-4306, hsa-miR-3158-5p, and hsa-miR-508-5p) were obtained from GSE63492 and GSE116726. It is functionally related to cell death, differentiation, transmembrane transport and tumorigenesis. Finally, we identified the following miRNA–mRNA regulatory networks: hsa-miR-508-5p-DRP2, hsa-miR-3158-ERBB2, hsa-miR-4306-POSTN and hsa-miR-5100-CAPRIN1. Subsequently, we verified our above findings using clinical IDD samples, senescent nucleus pulposus cell models, and IDD rat models.

Conclusions

These findings offer new insights into the occurrence and development of IDD and provide certain reference value for the subsequent diagnosis and treatment of IDD.