en عمومى General مقاله اصیل Original Article Background: Intervertebral disc degeneration (IDD) is a common disability in the working-age&nbsp;population. The underlying pathogenesis of IDD needs elucidation. This study aimed to determine&nbsp;differentially expressed circular RNAs (circRNAs) in IDD by bioinformatics. Additionally, the&nbsp;environmental and clinical factors involved in IDD pathogenesis were reviewed.<br> Methods: The circRNA array profiling of patients with IDD and healthy individuals (GSE67566) was&nbsp;acquired from Gene Expression Omnibus (GEO). GEO2R was employed to analyze the expression profiles of the circRNAs. Functional in silico analysis was done on circRNAs with the highest differential&nbsp;expression. Environmental and clinical factors were reviewed through PubMed and Google Scholar.<br> Results: Twenty-five circRNAs were differentially expressed in IDD. Two circRNAs (hsa_circRNA_101645 and hsa_circRNA_101852) exhibited the most downregulated and upregulated expressions. The functional in silico analysis showed that the aforementioned circRNAs harbored target<br> sites for AGO2 and EIF4A3 and several microRNAs. The upshots indicated that these 2 circular circRNAs might sponge hsa-miR-330-3p, hsa-miR-502-5p, hsa-miR-662, hsa-miR-874, and hsa-miR-646 and regulate PSD3, SIK2, PCYT1B, ARID5B, MTMR3, and HIPK2 expressions, which play significant roles<br> 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.<br> Conclusion: Although the results need confirmation by experimental analysis, they reflect the possible&nbsp;role of particular circRNAs in IDD pathogenesis. The controversy concerning the association between&nbsp;IDD and environmental and clinical factors necessitates in-depth population research. Investigating&nbsp;novel molecular regulatory markers like circRNAs could clarify the underlying molecular mechanisms of IDD. Intervertebral disc degeneration, Circular RNAs, Environmental factors 189 200 http://ehemj.com/browse.php?a_code=A-10-1021-2&slc_lang=en&sid=1 Mahshid Malakootian Mahshid.malakootian@gmail.com 100319475328460010336 100319475328460010336 No Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran Akram Gholipour akram.gholipour199069@gmail.com 100319475328460010337 100319475328460010337 No Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran Mahrokh Bagheri Moghaddam mahi.bagheri@gmail.com 100319475328460010338 100319475328460010338 No Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran Maedeh Arabian mdh_arabian@yahoo.com 100319475328460010339 100319475328460010339 No Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran Maziar Oveisee maziar.oveisee@gmail.com 100319475328460010340 100319475328460010340 Yes Corresponding author: Orthopedic Department, Bam University of Medical Sciences, Bam, Kerman, Iran