Dataset Information

A novel circRNA-miRNA-mRNA network reveals hsa-circ-0040039 as a biomarker for intervertebral disc degeneration.

ABSTRACT:

Objective

Alterations in the structure and function of intervertebral discs by multifaceted chronic processes can result in intervertebral disc degeneration (IDD). The mechanisms involved in IDD are still unknown.

Methods

We investigated the possible mechanisms underlying IDD using a bioinformatics analysis of publicly available microarray expression datasets and built a circular RNA-microRNA-mRNA (circRNA-miRNA-mRNA) network based on the results. Datasets GSE67566 and GSE116726 were downloaded from the Gene Expression Omnibus (GEO) and analyzed using the limma package in R. The CircInteractome database was used to detect miRNAs related to circRNA, and TargetScan, miRDB, and miRTarBase were used to predict target mRNAs. Key target genes were annotated using Gene Ontology terms.

Results

The circRNA hsa-circ-0040039 was found to have the top log fold-change score. Analysis using Metascape showed that the associated genes were enriched mainly in the cell cycle. The Cytoscape plugin MCODE predicted that two members of the RAS oncogene family-RAB1A and RAB1B-and multiple coagulation factor deficiency (MCFD2) may play key roles in IDD.

Conclusion

Our results suggested that hsa-circ-0040039 and the related network may be potential biomarkers for IDD.

SUBMITTER: Tang J

PROVIDER: S-EPMC8733709 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Accumulating evidence has indicated that noncoding RNAs are involved in intervertebral disc degeneration (IDD); however, the competing endogenous RNA (ceRNA)‑mediated regulatory mechanisms in IDD remain rarely reported. The present study aimed to comprehensively investigate the alterations in expression levels of circular RNA (circRNA), long noncoding RNA (lncRNA), microRNA (miRNA/miR) and mRNA in the nucleus pulposus (NP) of patients with IDD. In addition, crucial lncRNA/circRNA‑miRNA‑mRNA ceRNA interaction axes were screened using the GSE67567 microarray dataset obtained from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs) or genes (DEGs) between IDD and normal controls were identified using the Linear Models for Microarray data method. A protein‑protein interaction (PPI) network was constructed for DEGs based on protein databases, followed by module analysis. The ceRNA network was constructed based on the interaction between miRNAs and mRNAs, and lncRNAs/circRNAs and miRNAs. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery database. The present study identified 636 DECs, 115 DELs, 84 DEMs and 1,040 DEGs between patients with IDD and control individuals. PPI network analysis demonstrated that Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS), mitogen‑activated protein kinase 1 (MAPK1), hypoxia inducible factor 1 subunit α (HIF1A) and transforming growth factor β1 (TGFB1) were hub genes and enriched in modules. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1)/hsa_circRNA_102348‑hsa‑miR‑185‑5p‑TGFB1/FOS, MALAT1‑hsa‑miR‑155‑5p‑HIF1A, hsa_circRNA_102399‑hsa‑miR‑302a‑3p‑HIF1A, MALAT1‑hsa‑miR‑519d‑3p‑MAPK1 and hsa_circRNA_100086‑hsa‑miR‑509‑3p‑MAPK1 ceRNA axes were obtained by constructing the ceRNA networks. In conclusion, these identified ceRNA interaction axes may be crucial targets for the treatment of IDD.

Project description:Purpose To determine the repeatability of magnetic resonance (MR) elastography-derived shear stiffness measurements of the intervertebral disc (IVD) taken throughout the day and their relationship with IVD degeneration and subject age. Materials and Methods In a cross-sectional study, in vivo lumbar MR elastography was performed once in the morning and once in the afternoon in 47 subjects without current low back pain (IVDs = 230; age range, 20-71 years) after obtaining written consent under approval of the institutional review board. The Pfirrmann degeneration grade and MR elastography-derived shear stiffness of the nucleus pulposus and annulus fibrosus regions of all lumbar IVDs were assessed by means of principal frequency analysis. One-way analysis of variance, paired t tests, concordance and Bland-Altman tests, and Pearson correlations were used to evaluate degeneration, diurnal changes, repeatability, and age effects, respectively. Results There were no significant differences between morning and afternoon shear stiffness across all levels and there was very good technical repeatability between the morning and afternoon imaging results for both nucleus pulposus (R = 0.92) and annulus fibrosus (R = 0.83) regions. There was a significant increase in both nucleus pulposus and annulus fibrosus MR elastography-derived shear stiffness with increasing Pfirrmann degeneration grade (nucleus pulposus grade 1, 12.5 kPa ± 1.3; grade 5, 16.5 kPa ± 2.1; annulus fibrosus grade 1, 90.4 kPa ± 9.3; grade 5, 120.1 kPa ± 15.4), and there were weak correlations between shear stiffness and age across all levels (R ? 0.32). Conclusion Our results demonstrate that MR elastography-derived shear stiffness measurements are highly repeatable, weakly correlate with age, and increase with advancing IVD degeneration. These results suggest that MR elastography-derived shear stiffness may provide an objective biomarker of the IVD degeneration process. © RSNA, 2017 Online supplemental material is available for this article.

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