Circular RNA and intervertebral disc degeneration: unravelling mechanisms and implications

Abstract

Low back pain (LBP) is a major public health problem worldwide and a significant health and economic burden. Intervertebral disc degeneration (IDD) is the reason for LBP. However, we have not identified effective therapeutic strategies to address this challenge. With accumulating knowledge on the role of circular RNAs in the pathogenesis of IDD, we realised that circular RNAs (circRNAs) may have tremendous therapeutic potential and clinical application prospects in this field. This review presents an overview of the current understanding of characteristics, classification, biogenesis, and function of circRNAs and summarises the protective and detrimental circRNAs involved in the intervertebral disc that have been studied thus far. This review is aimed to help researchers better understand the regulatory role of circRNAs in the progression of IDD, reveal their clinical therapeutic potential, and provide a theoretical basis for the prevention and targeted treatment of IDD.

Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus

“…In recent years, several studies have identified various circRNAs related to the development of IVDD that function by targeting different miRNAs or RNA-binding proteins [ 16 , 17 , 18 , 19 , 20 ], thereby regulating diverse cellular activities. Previous research has shown that circFOXO3 is upregulated in different tissues and cells in response to exogenous ROS, and silencing circFOXO3 has been found to counteract the detrimental effects of ROS [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

“…Circular RNA (circRNA) is a distinct type of RNA that forms a circular construction by linking the 5′ and 3′ ends in a head-to-tail manner. Recent research has highlighted circRNAs role as microRNA (miRNA) sponges (a kind of competitive endogenous RNA mechanism) [ 16 , 17 , 18 , 19 , 20 ]. One particular circRNA of interest is circFOXO3, which originates from the back-splicing of the second exon of the forkhead box O3 ( FOXO3 ) gene.…”