Roles of circular RNAs in the pathogenesis of intervertebral disc degeneration (Review)

Abstract

Lower back pain (LBP) is an extremely common symptom and is recognized as a leading contributor to disability and disease burden globally. Intervertebral disc degeneration (IDD) represents a major cause of LBP. However, the molecular mechanisms involved in the pathogenesis of IDD remain unclear, and currently available treatments, including conservative and surgical options, fail to effectively delay, stop or reverse the progression of IDD. Circular RNAs (circRNAs) are a newly discovered group of covalently closed, single-stranded and endogenous non-coding RNAs. A growing body of research has revealed that a number of circRNAs are widely and aberrantly expressed in IDD tissues. Furthermore, they play important roles in the pathogenesis of IDD, including proliferation, apoptosis, senescence, mitophagy, inflammation and extracellular matrix metabolism, mainly by acting as sponges for microRNAs. The present review aims to summarize the current understanding on the mechanisms of circRNA-mediated regulation in IDD.

Role of hippocampal circKcnk9 in visceral hypersensitivity and anxiety comorbidity of irritable bowel syndrome

“…Different circRNAs may play different roles in chronic pain and negative emotions. For example, circ-Ankib1 and circAnks1a are involved in the development of neuropathic pain (Zhang S. B. et al, 2019 ); circRNA_104670 and circSEMA4B are involved in low back pain (Lin et al, 2021 ); circSlc7a11 overexpression is involved in bone cancer pain (Chen et al, 2021 ); and circSTAG1 was significantly decreased in the hippocampus of chronic unpredictable stress-treated mice and the peripheral blood of patients with major depressive disorder (Huang et al, 2020 ). These studies indicate that the roles of different circRNAs are relatively specific and could potentially be used for disease diagnosis and treatment.…”

Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying circ_0050205 Attenuate Intervertebral Disc Degeneration

“…BMSCs secrete EVs that can shuttle their cargos, such as circRNAs, between cells. Many circRNAs act importantly in the pathogenesis of IDD through acting as sponges for miRNAs [ 37 ]. As the obtained findings demonstrated, circ_0050205, a circRNA of interest, could be transferred from BMSCs into NPCs via EVs and then increase NPC survival and inhibit ECM degradation by binding to miR-665 and upregulating GPX4 expression.…”

Extracellular Non-Coding RNAs in Cardiovascular Diseases

“…Recent evidence has identified a crucial role of several extracellular circRNAs in alleviating damage due to cardiomyocyte hypertrophy, heart failure (HF), myocardial infarction (MI), and dysfunction caused by ischemia-reperfusion (I/R) [ 26 ]. Furthermore, several studies have also reported their association with proliferation, apoptosis, and inflammatory responses, thus influencing physiological and pathological phenomena in various tissues [ 7 , 27 ]. Investigation of circRNAs continues to elucidate their role in the pathogenesis of CVDs and provides a potential avenue for therapeutic development.…”

“…Ex-ncRNAs are a heterogeneous group of RNAs, including small ncRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), which encompass the majority of the extracellular transcriptome [ 7 , 8 ]. Ex-ncRNAs can be translocated into receipt cells after being secreted into the extracellular space through a variety of methods, thereby regulating various biological processes in targeted cells under both physiological and pathological conditions [ 9 ] ( Figure 1 ).…”