Potential Roles of Circular RNAs and Environmental and Clinical Factors in Intervertebral Disc Degeneration

Background: Intervertebral disc degeneration (IDD) is a common disability in the working-age population. The underlying pathogenesis of IDD needs elucidation. This study aimed to determine differentially expressed circular RNAs (circRNAs) in IDD by bioinformatics. Additionally, the environmental and clinical factors involved in IDD pathogenesis were reviewed. Methods: The circRNA array profiling of patients with IDD and healthy individuals (GSE۶۷۵۶۶) was acquired from Gene Expression Omnibus (GEO). GEO۲R was employed to analyze the expression profiles of the circRNAs. Functional in silico analysis was done on circRNAs with the highest differential expression. Environmental and clinical factors were reviewed through PubMed and Google Scholar. Results: Twenty-five circRNAs were differentially expressed in IDD. Two circRNAs (hsa_circRNA_۱۰۱۶۴۵ and hsa_circRNA_۱۰۱۸۵۲) exhibited the most downregulated and upregulated expressions. The functional in silico analysis showed that the aforementioned circRNAs harbored target sites for AGO۲ and EIF۴A۳ and several microRNAs. The upshots indicated that these ۲ circular circRNAs might sponge hsa-miR-۳۳۰-۳p, hsa-miR-۵۰۲-۵p, hsa-miR-۶۶۲, hsa-miR-۸۷۴, and hsa-miR-۶۴۶ and regulate PSD۳, SIK۲, PCYT۱B, ARID۵B, MTMR۳, and HIPK۲ expressions, which play significant roles in autophagy and cellular senescence. Temperature, heavy metal exposure, age, overweight, occupation, exercise, hypertension, and smoking were the environmental and clinical factors associated with IDD progression. Conclusion: Although the results need confirmation by experimental analysis, they reflect the possible role of particular circRNAs in IDD pathogenesis. The controversy concerning the association between IDD and environmental and clinical factors necessitates in-depth population research. Investigating novel molecular regulatory markers like circRNAs could clarify the underlying molecular mechanisms of IDD.

Keywords:

Intervertebral disc degeneration , Circular RNAs , Environmental factors