Search

Circular RNAs (circRNAs) are non-coding RNAs that exist naturally in various eukaryotic organisms. The majority of circRNAs are produced through the splicing of exons, although there are a limited number that are generated through the circularization of introns. Studies have shown that circRNAs play an irreplaceable role in the pathogenesis, disease progression, diagnosis, and targeted therapy of motor system tumors (osteosarcoma), metabolic diseases (osteoporosis), and degenerative diseases (osteonecrosis of the femoral head, osteoarthritis, intervertebral disc degeneration). This review summarizes the advancements in circRNA detection techniques and the research progress of circRNAs in orthopedic diseases.

BackgroundOsteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a key gene in mediating the formation of the stabilized collagen cross-link, playing an important role in the progression of cancer. However, the interaction between OS and PLOD2 has not been clarified so far.MethodsThe target gene PLOD2 was screened through our own RNA-seq results and other two RNA-seq results from GEO database. The expression of PLOD2 in OS was detected by RT-qPCR, Western blot and immunohistochemistry. Functional experiments were performed to investigate the role of PLOD2 in OS cell invasion, migration and angiogenesis in vitro. An OS lung metastasis model was established to investigate the function of PLOD2 in OS metastasis and angiogenesis in vivo. The role of PLOD2 in immune infiltration in OS was explored by KEGG/GO analysis and immune infiltration analysis with TARGET, TCGA and TIMER.ResultsPLOD2 was high-expressed in OS, which was related to poor prognosis of OS patients. PLOD2 promoted OS cell migration, invasion and angiogenesis in vitro and aggravated OS metastasis and angiogenesis in vivo. Bioinformatic analysis showed that PLOD2 played an important role in immune cell infiltration in OS, including CD8 positive T cells, macrophages M0 cells, DC cells, endothelial cells, iDC cells, ly endothelial cells, MEP cells, mv endothelial cells, native B cells, smooth muscle cells and Th1 cells. Immunohistochemical results showed that the expression of CD4 and CD8A was negatively correlated with the expression of PLOD2 in OS.ConclusionPLOD2 was high-expressed in OS and promoted OS migration, invasion and angiogenesis in vitro and facilitated OS metastasis and angiogenesis in vivo. PLOD2 was associated with immune cell infiltration in OS, which could be a promising target to treat OS patients with metastasis and utilized to guide clinical immunotherapy in the future.