The role of circRNA derived from RUNX2 in the serum of osteoarthritis and its clinical value

Abstract

Background Circular RNA (circRNA) has been shown to affect the pathological process of osteoarthritis (OA) and is expected to become a potential marker for disease diagnosis. This study aimed to investigate the association between circRNA derived from the gene of runt‐related transcription factor 2 (RUNX2) and OA risk. Methods The expression profile of RUNX2‐derived circRNAs in serum of OA patients was detected. Then, the cytological localization of screened differential circRNAs was studied. Luciferase (LUC) reporter assay was used to identify the microRNA (miRNA) sponge capacity of the circRNAs. Bioinformatics analysis was used to construct the functional pathway of this circRNA‐miRNAs network. And then, the diagnostic value of RUNX2‐derived circRNAs in OA was evaluated. Results RUNX2‐derived hsa_circ_0005526 (circ_RUNX2) is significantly highly expressed in OA serum and mainly located in the cytoplasm within the cartilage cell by sponging multiple miRNAs (miR‐498, miR‐924, miR‐361‐3p, and miR‐665). Bioinformatics analysis showed ECM‐receptor interaction pathway ranked the most significant pathway of circ_RUNX2‐miRNAs regulatory network in KEGG database. The ROC curve showed that there may be good diagnostic value of serum circ_RUNX2 in OA. Conclusion RUNX2‐derived circ_RUNX2 may be involved in OA development via ECM‐receptor interaction pathways and may be used as potential clinical indicator of OA.

Circ_0005526 contributes to interleukin-1β-induced chondrocyte injury in osteoarthritis via upregulating transcription factor 4 by interacting with miR-142-5p

“… The previous study indicated that circ_0005526 was upregulated in serum of OA patients, and had clinical significance in OA [ 10 ]. Our evidences unraveled that circ_0005526 knockdown inhibited chondrocyte injury in IL-1β-induced OA model through mediating miR-142-5p/TCF4 axis.…”

“…elucidated that circ_0134111 aggravated inflammatory reaction and extracellular matrix degradation of chondrocytes in OA through downregulating suppressor of cytokine signaling 1 (SOCS1) by targeting miR-515-5p [ 9 ]. Circ_0005526 has been shown to function as miRNA sponges in OA [ 10 ], but the regulatory function of circ_0005526 remains unknown.…”

Knockdown of Circ_0037658 Alleviates IL-1β-Induced Osteoarthritis Progression by Serving as a Sponge of miR-665 to Regulate ADAMTS5

“…In this paper, miR-665 was of particular interest among putative target miRNAs of circ_0037658. MiR-665 has been confirmed to play an important role in the circ_RUNX2-miRNA’s regulatory network in OA progression ( Wang C. et al, 2021 ). Furthermore, the dysregulation of miR-665 was closely associated with IL-1β-triggered cell damage in some relevant literature ( Wang et al, 2020 ; Ouyang et al, 2021 ).…”

The Application of circRNA-016901 in Improving the Diagnostic Accuracy of Osteoarthritis

“…Although previous studies have reported the application of circRNAs as biomarkers for the diagnosis of OA [ 22 , 23 ], these studies only included HCs as true negative cases in ROC curve analysis. For instance, using increased serum expression levels of circ_RUNX2 as a biomarker, patients with OA were separated from controls [ 22 ]. In another study, the application of blood hsa_circ_0032131 in separating OA patients from the controls has also been investigated [ 23 ].…”