Abstract
Osteosarcoma (OS) is a common malignant tumor in the world. Circular RNAs are endogenous non-coding RNAs that have been linked to the development of cancer. However, the role of circ_001569 in OS progression is still unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_001569, microRNA-185-5p (miR-185-5p) and flotillin-2 (FLOT2). The abilities of cell proliferation, migration and invasion were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Also, western blot analysis was performed to assess the levels of epithelial–mesenchymal transition (EMT)-related proteins and FLOT2 protein. Besides, the dual-luciferase reporter assay was used to verify the interactions among circ_001569, miR-185-5p and FLOT2. Circ_001569 expression was increased in OS tissues and cells, and its knockdown reduced the proliferation, migration, invasion and EMT of OS cells. MiR-185-5p could interact with circ_001569. Inhibition of miR-185-5p could recover the suppression effects of silenced-circ_001569 on the proliferation and metastasis of OS cells. Furthermore, FLOT2 was a target of miR-185-5p. Overexpressed FLOT2 could restore the inhibition effects of miR-185-5p mimic on the proliferation and metastasis of OS cells. Also, FLOT2 expression was regulated by circ_001569 and miR-185-5p. In addition, circ_001569 knockdown also reduced the OS tumor growth in vivo. Circ_001569 might act as an oncogene in OS progression by regulating the miR-185-5p/FLOT2 axis, which provided a reliable new approach for the treatment of OS patients.
Highlights
Osteosarcoma (OS) is a malignant bone tumor originating from stromal cells and usually occurs in adolescents and children under 20 years of age [1,2]
The MTT assay was used to assess the proliferation of OS cells
We further conducted Western blot (WB) analysis to evaluate the changes of epithelial–mesenchymal transition (EMT)-related proteins in OS cells
Summary
Osteosarcoma (OS) is a malignant bone tumor originating from stromal cells and usually occurs in adolescents and children under 20 years of age [1,2]. The exploration of new mechanisms affecting OS metastasis is expected to provide new ideas for reducing the death rate of OS. In OS, Xi et al identified a total of 259 differentially expressed circRNAs and found through gene ontology function enrichment analysis that they had significant enrichment in cell biological processes, cellular components and molecular functions [12]. This suggested that circRNA played an essential role in OS progression. It had been found that high expression of circ_001569 was related to the progression of non-small cell lung cancer and hepatocellular carcinoma [13,14]. The effect of circ_001569 on the metastasis of OS and its molecular mechanism have not been investigated
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