CircSERPINE2 protects against osteoarthritis by targeting miR-1271 and ETS-related gene

Abstract

ObjectivesCircular RNAs (circRNA) expression aberration has been identified in various human diseases. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of osteoarthritis (OA).MethodsCircRNA deep sequencing was performed to the expression of circRNAs between OA and control cartilage tissues. The regulatory and functional role of CircSERPINE2 upregulation was examined in OA and was validated in vitro and in vivo, downstream target of CircSERPINE2 was explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence in situ hybridisation were used to evaluate the interaction between CircSERPINE2 and miR-1271-5 p, as well as the target mRNA, E26 transformation-specific-related gene (ERG). The role and mechanism of CircSERPINE2 in OA was also explored in rabbit models.ResultsThe decreased expression of CircSERPINE2 in the OA cartilage tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix (ECM). Mechanistically, CircSERPINE2 acted as a sponge of miR-1271-5 p and functioned in human chondrocytes (HCs) through targeting miR-1271-5 p and ERG. Intra-articular injection of adeno-associated virus-CircSERPINE2-wt alleviated OA in the rabbit model.ConclusionsOur results reveal an important role for a novel circRNA-CircSERPINE2 in OA progression. CircSERPINE2 overexpression could alleviate HCs apoptosis and promote anabolism of ECM through miR-1271-ERG pathway. It provides a potentially effective therapeutic strategy for OA progression.

miR‐142‐5p protects against osteoarthritis through competing with lncRNA XIST

“…miRNA‐103 is also reported to target Sox6 and facilitate OA development . Similarly, multiple types of noncoding RNAs have been investigated and identified by RNA sequencing in diseases with OA progression, including long intergenic noncoding RNAs, antisense RNAs and circular RNAs (circRNAs) . Of note, the wide existence of long non‐coding RNAs (lncRNAs) is accepted in eukaryotic cells.…”

“…13 Similarly, multiple types of noncoding RNAs have been investigated and identified by RNA sequencing in diseases with OA progression, including long intergenic noncoding RNAs, antisense RNAs and circular RNAs (cir-cRNAs). [14][15][16][17] Of note, the wide existence of long non-coding RNAs Mechanistically, recent studies show that several lncRNAs or cir-cRNAs, harboring miRNA-binding sites, are capable of functioning as competing endogenous RNAs (ceRNAs) to naturally sequester miRNA away from target mRNA and competitively block the inhibitory impact of miRNA on mRNA. 18 As explained previously, SNHG16 can block the inhibition of miR-205 on Smad2 expression in aortic smooth muscle cell proliferation and migration.…”

CircGCN1L1 promotes synoviocyte proliferation and chondrocyte apoptosis by targeting miR-330-3p and TNF-α in TMJ osteoarthritis

“…Circular RNAs are a type of endogenous noncoding RNA that performs very important roles in OA progression 8,36 . Several studies have reported differential expression of circRNAs in OA cartilage and their potential to regulate the vitality and functions of chondrocytes 11,37 . However, little is known about the roles of circRNAs in the articular synovium.…”

Noncoding RNAs: New regulatory code in chondrocyte apoptosis and autophagy

“…For instance, ciRS‐7 promoted the proliferation of chondrocytes in an IL‐1β‐induced OA model via negatively regulating miR‐7 (Zhou, Jiang, et al, ). circRNA‐CER, hsa_circ_0045714, and circSERPINE2 regulate the biosynthesis of the ECM and promote the proliferation of chondrocytes by negatively regulating miR‐136, and activating the miR‐193b/IGF1R and miR‐1271‐5p/ERG axes (Li, Zhang, Xiao, et al, ; Liu, Zhang, et al, ; Shen et al, ). Therefore, abnormally expressed circRNAs in OA‐affected chondrocytes play important roles in the onset and development of OA by inducing or inhibiting chondrocyte apoptosis.…”