Construction of a lncRNA-miRNA-mRNA Network for Biomarker Identification in Intervertebral Disc Degeneration.

Objective: To identify pivotal gene markers and pathways involved in intervertebral disc degeneration (IDD) through the construction of a competing endogenous RNA (ceRNA) network.

Methods: A ceRNA network was constructed using mRNAs associated with clinical IDD phenotypes (age, MRI grade), identified through Weighted Gene Co-expression Network Analysis (WGCNA). From the core mRNAs within the ceRNA network, potential marker genes were identified using LASSO regression, Support Vector Machine (SVM), and Random Forest algorithms. A sub-network was then constructed, and the candidate marker genes were further validated using the mouse IDD dataset GSE134955.

Results: A total of 119 differentially expressed long non-coding RNAs (DELs), 1,267 differentially expressed mRNAs (DEMs), and 37 differentially expressed microRNAs (DEMis) were identified in IDD samples compared to controls. WGCNA identified 1,190 DEMs significantly associated with MRI grade. Based on these MRI grade-associated DEMs, a hub ceRNA network comprising 4 DEMis, 90 DELs, and 18 DEMs was established. Among these, three DEMs-BTG2, MDM4, and ACOX1-were consistently identified as marker genes by LASSO, SVM, and Random Forest. These three genes also demonstrated high accuracy in distinguishing IDD from control samples in the independent mouse dataset.

Conclusion: This study identified key mRNAs implicated in IDD progression and provides new insights into the regulatory roles of ceRNA networks in the disease. These findings may contribute to the development of novel diagnostic biomarkers and therapeutic targets for IDD.