Peripheral neuropathy (PN) is an incurable complication of multiple myeloma (MM) which adversely affects patients' quality of life. The important roles that Circular RNAs (circRNAs) play in tumor progression, and exosome-mediated intracellular communication has been recognized as a crucial factor in the pathogenesis of MM. However, the role of exosome-derived circRNAs (exo-circRNAs) in MM and MM-induced PN remains elusive. In this study, we aimed to investigate the correlation between serum exo-circRNAs and MM to preliminarily explore the role of exo-circRNAs in MM-related PN. A cohort of 25 MM patients and 5 healthy control (HC) individuals were enrolled in the study. High-throughput sequencing and qRT PCR validation of serum exo-circRNAs were used to generate the aberrantly expressed exo-circRNAs profiles. Bioinformatics analysis was done using GO, KEGG, miRanda, Targetscan and Metascape. Correlation analysis was conducted between chr2:2744228–2,744,407+ and clinical characteristics of PN. ROC curve, univariate and multivariate COX regression models were conducted to identify the prognostic potential of chr2:2744228–2,744,407+ in the MM-related PN. 265 upregulated circRNAs and 787 downregulated circRNAs, with at least a two-fold difference in expression level in MM patients vs HC, were screened. Bioinformatics analysis indicated that upregulated circRNAs had the potential to facilitate MM-related PN. Furthermore, PCR validated the abundant expression of chr2:2744228–2,744,407+ in the serum exosomes of 25 MM patients. Bioinformatics analysis indicated that chr2:2744228–2,744,407+ might induce MM related PN via the downstream miRNA and GRIN2B axis. Overexpressed chr2:2744228–2,744,407+ in the serum exosomes of MM patients might lead to the downregulation of hsa-miR-6829-3p, elevation of GRIN2B in the serum and PC12 cells, and inhibited cell viability. The correlation analysis indicated that the expression of chr 2:2744228–2,744,407+ was positively correlated with the clinical characteristics of PN. ROC curve, univariate and multivariate COX regression analysis identified that chr2:2744228–2,744,407+ is an independent prognostic factor in the MM related PN. We identified that the abnormal expression of the serum exo-circRNA was correlated with MM-related PN, implying that exo-circRNA has potential as a novel therapeutic target for MM related PN.

周围神经病变 (PN) 是多发性骨髓瘤 (MM) 的一种无法治愈的并发症，会对患者的生活质量产生不利影响。环状RNA（circRNA）在肿瘤进展和外泌体介导的细胞内通讯中发挥的重要作用已被认为是MM发病机制的关键因素。然而，外泌体衍生的circRNA（exo-circRNAs) 在 MM 和 MM 诱导的 PN 中仍然难以捉摸。本研究旨在探讨血清exo-circRNAs与MM的相关性，初步探讨exo-circRNAs在MM相关PN中的作用。该研究招募了 25 名 MM 患者和 5 名健康对照 (HC) 个体。血清exo-circRNAs的高通量测序和qRT PCR验证用于生成异常表达的exo-circRNAs谱。使用 GO、KEGG、miRanda、Targetscan 和 Metascape 进行生物信息学分析。在 chr2:2744228–2,744,407+ 与 PN 的临床特征之间进行了相关分析。进行了 ROC 曲线、单变量和多变量 COX 回归模型来确定 chr2:2744228–2,744,407+ 在 MM 相关 PN 中的预后潜力。265 个上调的 circRNA 和 787 个下调的 circRNA，筛选出 MM 患者与 HC 的表达水平至少有两倍差异。生物信息学分析表明，上调的 circRNA 有可能促进 MM 相关的 PN。此外，PCR 验证了 chr2:2744228–2,744,407+ 在 25 名 MM 患者的血清外泌体中的丰富表达。生物信息学分析表明 chr2:2744228–2,744,407+ 可能通过下游 miRNA 和 GRIN2B 轴诱导 MM 相关 PN。MM患者血清外泌体中过度表达的chr2:2744228-2,744,407+可能导致hsa-miR-6829-3p下调，血清和PC12细胞中GRIN2B升高，抑制细胞活力。相关分析表明chr 2:2744228-2,744,407+的表达与PN的临床特征呈正相关。ROC曲线，单变量和多变量 COX 回归分析确定 chr2:2744228–2,744,407+ 是 MM 相关 PN 的独立预后因素。我们发现血清的异常表达exo- circRNA 与 MM 相关 PN 相关，这意味着 exo-circRNA 具有作为 MM 相关 PN 新治疗靶点的潜力。