Abstract
Osteosarcoma is the most common primary malignant tumor, especially in children and adolescents. Circular RNAs (circRNAs) are found to play roles in the progression of osteosarcoma. However, the exact functions of circRNAs in osteosarcoma development still need to be clarified. We obtained differentially expressed circRNAs and miRNAs from a GSE99671 data set (GEO database). The gene co-expression network of ceRNAs and osteosarcoma-related genes was analyzed using the STRING database. qRT-PCR was used to detect the expression of circ-03955 and miR-3662. Transwell assays and flow cytometry were performed to detect phenotypic changes in cell function. A xenograft tumor model was established using BALB/c nude mice. Dual luciferase activity and RNA immunoprecipitation assays were performed to assess the relationship between circ-03955, miR-3662, and metadherin (MTDH). Immunohistochemistry, immunofluorescence, and Western blotting were used to assess protein expression levels. Circ-03955 was significantly upregulated, and miR-3662 was downregulated in osteosarcoma. Circ-03955 silencing inhibited the growth and metastasis of osteosarcoma. Mechanism analysis revealed that circ-03955 could bind to miR-3662, and the latter could target MTDH, leading to its suppressed expression and facilitating epithelial-mesenchymal transition (EMT). All these findings demonstrate that the presence of circ-03955 promotes EMT in osteosarcoma by acting as miR-3662 sponge-mediated MTDH expression.
Highlights
Osteosarcoma is the most common malignant bone neoplasm, especially in children and adolescents
The ceRNA network map was analyzed using co-expression analysis, and the results show that MTDH and circ-03955 play an important role in the graph (Figure 1D)
The expression of circ-03955, MTDH, and miR-3662 was found to be inversely correlated in osteosarcoma tissues (Figure 1E)
Summary
Osteosarcoma is the most common malignant bone neoplasm, especially in children and adolescents. It has a high rate of mortality and disability [1, 2] as well as high levels of metastasis and invasion. Circular RNA (circRNA) is a relatively newly identified form of RNA. In 2012, Salzman [5] found that many highly expressed circRNAs are associated with their corresponding linear RNA, which can form multiple homotypes of circular RNA by “non-classical splicing,” and speculated that the expression of circRNA might be a general pattern of gene expression program in human cells. Studies show that circRNA can regulate the proliferation and apoptosis of osteosarcoma and are good targets for clinical diagnosis [13,14,15]. The effect of circRNA on osteosarcoma has not been studied in detail
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