(1) Background: At present,
cancer cell
metastasis is the main cause of death in patients with malignant
tumors, and up to 23% of
osteosarcoma patients have died due to lung and
lymph node metastasis. Therefore, finding new molecules involved in
tumor development can provide new strategies for the diagnosis and treatment of
osteosarcoma patients.
Circular RNAs (
circRNAs) are a type of
RNA molecule that are connected head-to-tail to form a closed ring. There is increasing evidence that
circRNAs are
RNA molecules with many
biological functions in various diseases. However, the role and mechanism of
circRNAs in
osteosarcoma have rarely been reported. (2) Methods: The expression of circSRSF4 in
osteosarcoma tissues and cell lines was detected by quantitative real-time PCR (RT-qPCR), and the result of high-throughput sequencing was verified. In order to explore the effect of circSRSF4 on
tumor proliferation, invasion, and migration, a dual-
luciferase reporter assay,
RNA binding protein immunoprecipitation assay, cell counting kit-8 (CCK-8), transwell assay, scratch wound healing assay, Western blot analysis, and other experiments were carried out in vitro. Rescue experiments and a xenograft model confirmed that circSRSF4 directly acted on miR-224 to regulate Rac1 expression. (3) Results: The expression of circSRSF4 was significantly higher in
osteosarcoma tissues and cell lines. Down-regulating the expression of circSRSF4 in vitro significantly inhibited the proliferation, invasion, and migration of cells, and also reduced the expression of Rac1, while the overexpression of Rac1 and miR-224 inhibition could reverse these effects. The inhibition of circSRSF4 expression in vivo also attenuated
tumor growth. A mechanistic study showed that circSRSF4 can be used as an miR-224 sponge to up-regulate the expression of Rac1, thereby promoting the development of
osteosarcoma. (4) Conclusions: CircSRSF4 acting as a
ceRNA promotes the malignant behavior of
osteosarcoma through the circSRSF4/miR-224/Rac1 axis, which provides a new theoretical basis for the clinical prevention and treatment of
osteosarcoma and the study of related markers and intervention targets.