Circular RNA hsa_circ_0005909 modulates osteosarcoma progression via the miR-936/HMGB1 axis

环状 RNA hsa_circ_0005909 通过 miR-936/HMGB1 轴调节骨肉瘤进展

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作者:Shuai Ding, Guangquan Zhang, Yanzheng Gao, Shulian Chen, Chen Cao

Background

Osteosarcoma (OS) is the most common bone malignant tumor in children, youth, and adolescents. Circular RNA hsa_circ_0005909 (circ_0005909) is involved in the progression of OS. Nevertheless, there are few reports on the role and mechanism of circ_0005909 in OS.

Conclusions

Circ_0005909 inhibition impeded the progression of OS via downregulating HMGB1 via sponging miR-936.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to examine the expression of circ_0005909, miR-936, and High Mobility Group Box 1 (HMGB1) mRNA in OS tissues and cells. Cell viability, colony formation, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), cell colony formation, or transwell assays. Cell epithelial-mesenchymal transition (EMT) and HMGB1 protein levels were assessed through western blot analysis. The role of circ_0005909 on tumor growth in vivo was verified by xenograft assay. The relationship between circ_0005909 or HMGB1 and miR-936 was confirmed with the dual-luciferase reporter or RNA pull-down assays.

Results

Circ_0005909 level was upregulated in OS tissues and cells. OS patients with high circ_0005909 expression had a lower survival rate. Circ_0005909 inhibition reduced tumor growth in vivo and constrained cell viability, colony formation, migration, invasion, and EMT of OS cells in vitro. Furthermore, circ_0005909 served as a sponge for miR-936 and the repressive impacts of circ_0005909 silencing on malignant behaviors of OS cells were abolished by miR-936 inhibitors. Also, HMGB1 acted as a target for miR-936 and was modulated by circ_0005909 via miR-936. Additionally, HMGB1 overexpression restored the inhibitory influence on the malignant behaviors of OS cells mediated by circ_0005909 inhibition. Conclusions: Circ_0005909 inhibition impeded the progression of OS via downregulating HMGB1 via sponging miR-936.

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