hsa_circ0021347 as a Potential Target Regulated by B7-H3 in Modulating the Malignant Characteristics of Osteosarcoma

Abstract

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.

Emerging landscape of circular RNAs as biomarkers and pivotal regulators in osteosarcoma

“…As mentioned above, B7‐H3 is a negative regulator in osteoimmunology. A recent study showed that B7‐H3 knockdown could modulate circ0021347 and thereby affect osteosarcoma malignancy (L. Wang, Zhang, et al, 2019). Comprehensive understanding of the circRNA regulatory network in OS could provide us with more information to utilize circRNAs' potential in clinical application.…”

“…B7‐H3 (CD276), a membrane protein of B7 family members and costimulatory molecular, serves as a critical negative regulator in immune response in osteosarcoma by facilitating tumor cells to escape from immunosurveillance (He & Li, 2019; L. Wang, Zhang, Kang, Zhang, & Zhang, 2019). A previous study showed an abnormal expression pattern of B7‐H3 in osteosarcoma, which may partially contribute to its immune escape, cell growth and invasive ability (L. Wang, Kang, et al, 2018; L. Wang, Zhang, et al, 2019). Through circRNA screening, L. Wang, Zhang, et al, 2019) identified that circ0021347 was markedly downregulated in osteosarcoma and may be a potential downstream target gene of B7‐H3.…”

“…A previous study showed an abnormal expression pattern of B7‐H3 in osteosarcoma, which may partially contribute to its immune escape, cell growth and invasive ability (L. Wang, Kang, et al, 2018; L. Wang, Zhang, et al, 2019). Through circRNA screening, L. Wang, Zhang, et al, 2019) identified that circ0021347 was markedly downregulated in osteosarcoma and may be a potential downstream target gene of B7‐H3. Intriguingly, the detailed molecular mechanism of the crosstalk between circ0021347 with B7‐H3 in osteosarcoma progression remains unknown and requires further exploration.…”

Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma

“…Moreover, 22 studies were further eliminated with a variety of reasons, including ve studies not related to circRNAs or osteosarcoma, six studies did not report outcomes, two reviews and case reports, four animal studies, and ve lack of extractable data. Finally, 26 studies comprising 1,652 osteosarcoma cases were enrolled in this quantitative study, with 18 on clinicopathological features, ten on diagnosis [13,18,19,21,24,[30][31][32][33][34] [12,14,18,19,[32][33][34][36][37][38][39][40], whereas other two studies on downregulated circRNAs applying ≥ 18 or < 18 years old to separate enrolled patients [13,30]. In consideration of the consistency, only these studies with common cut-off value were included in the following meta-analysis with regard to patients' age.…”

“…CircRNAs were regarded as oncogenes or tumor-suppressor in terms of their expression levels. Speci cally, 21 circRNAs were identi ed as oncogenic circRNAs with upregulated expression pattern [12, 14, 16-23, 31-34, 36, 37, 39-43], while the other ve were recognized as tumor suppressors [13,24,30,35,38] with downregulated expression, respectively. The duration for follow-up ranged from 40 to 125.…”