In our previous study, we showed that B7-H3 played crucial roles in osteosarcoma (OS) development and might serve as a negative regulator of in osteoimmunology and help tumor cells escape immune surveillance. However, little is known about B7-H3 deficiency and its corresponding circRNA alteration or their relationship with osteosarcoma progression. erefore, we established stable silencing of B7-H3 in OS cells and validated our results with western blotting and real-time PCR detection. en, we performed a circRNA array to analyze the differential expression of circRNAs between the control and B7-H3 knockdown cells. e association between target circRNA expression and the clinicopathological features of patients with OS was further analyzed. As a result, hsa_circ0021347 was selected and validated to be significantly downregulated in OS tissues and cell lines and showed a strong negative relationship with B7-H3 expression in OS. In addition, clinicopathological features showed that hsa_circ0021347 in OS tissues was negatively associated with Enneking stage and positively associated with patients' survival. Finally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and PANTHER pathway analyses were performed to predict a network of hsa_circ0021347/miRNAs interactions to help us develop potential biomarkers for clinical diagnosis and design therapeutic strategies for OS.
Sialic acid-binding receptors are expressed on the surfaces of a variety of immune cells and have complex and diverse immunoregulatory functions in health and diseases. Recent studies have shown that Siglecs could play diverse immune and nonimmune regulatory roles in the tumor microenvironment (TME) and participate in tumor progression through various mechanisms, such as regulating tumor growth and metastasis, mediating the inflammatory response, and promoting tumor immune escape, thereby affecting the prognoses and outcomes of patients. However, depending on the cell type in which they are expressed, each Siglec member binds to corresponding ligands in the microenvironment milieu to drive diverse cell physiological and pathological processes in tumors. Therefore, we herein summarize the expression spectra and functions of the Siglec family in human diseases, particularly cancer, and highlight the possibility of therapeutic interventions targeting the TME in the future.
The main features of a giant cell tumor of bone (GCTB) are frequent recurrence and aggressive osteolysis, which leads to a poor prognosis in patients. Although the treatment methods for a GCTB, such as scraping and resection, effectively inhibit the disease, the tendency toward malignant transformation remains. Therefore, it is important to identify new treatment methods for a GCTB. In this study, we first found high Siglec-15 expression in GCTB tissues, which was significantly associated with Campanacci staging and tumor recurrence. In Spearman’s analysis, Siglec-15 expression was significantly correlated with Ki-67 levels in tumor tissues. In vitro, the mRNA and protein levels of Siglec-15 were high in GCTB stromal cells (Hs737. T), and Siglec-15 knockdown inhibited the biological characteristics of GCTB stromal cells. The RNA sequencing results enabled a prediction of the downstream genes by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and MCODE analyses, and the findings showed that CXCL8 was significantly regulated by Siglec-15 and might be a promising downstream target gene of Siglec-15. Therefore, Siglec-15 may be a potential immunotherapy target for a GCTB.
Although the mortality rate of osteosarcoma (OS) patients has improved, there are still many unsolved problems concerning how to reduce recurrence and metastasis. In the tumor microenvironment, immune escape plays a more important role in tumor progression and development. Many costimulatory molecules of the B7 family have been reported to be involved in regulating immunological interactions between OS cells and immune cells. Among these molecules, B7-H1 and its receptor, programmed death-1 (PD-1), have been the focus of the fields of tumor immunology and have been recently applied in clinical trials of therapies for several solid tumors. These therapies, referred to as B7-H1/PD-1 checkpoint blockade therapies, are designed to block the interaction between the two molecules. Although the mechanism has been reported in some malignancies, the specific impact of B7-H1/PD-1 expression on OS has not been well defined. Here, we review the expression, function, and regulatory mechanism of the B7-H1/PD-1 axis in OS and introduce and compare the advantages and disadvantages of B7-H1/PD-1 immunotherapies in OS.
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