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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Dai, Hongchun Yi, Guangming Jiang, Dong Min, Yanmei Li, Zongwei |
| Abstract | Background Many studies have confirmed that circular RNAs (circRNAs) mediate the malignant progression of various tumors including osteosarcoma (OS). Our study is to uncover novel molecular mechanisms by which circ_0000376 regulates OS progression. Methods The expression of circ_0000376, microRNA (miR)-577, hexokinase 2 (HK2) and lactate dehydrogenase-A (LDHA) was determined by quantitative real-time PCR. OS cell proliferation, apoptosis and invasion were measured using cell counting kit 8 assay, colony formation assay, EdU assay, flow cytometry and transwell assay. Besides, cell glycolysis was assessed by testing glucose consumption, lactate production, and ATP/ADP ratios. Protein expression was examined by western blot analysis. The interaction between miR-577 and circ_0000376 or HK2/LADA was verified by dual-luciferase reporter assay. The role of circ_0000376 on OS tumor growth was explored by constructing mice xenograft models. Results Circ_0000376 had been found to be upregulated in OS tissues and cells. Functional experiments revealed that circ_0000376 interference hindered OS cell growth, invasion and glycolysis. Circ_0000376 sponged miR-577 to reduce its expression. In rescue experiments, miR-577 inhibitor abolished the regulation of circ_0000376 knockdown on OS cell functions. MiR-577 could target HK2 and LDHA in OS cells. MiR-577 suppressed OS cell growth, invasion and glycolysis, and these effects were reversed by HK2 and LDHA overexpression. Also, HK2 and LDHA expression could be regulated by circ_0000376. In vivo experiments showed that circ_0000376 knockdown inhibited OS tumorigenesis. Conclusion Circ_0000376 contributed to OS growth, invasion and glycolysis depending on the regulation of miR-577/HK2/LDHA axis, providing a potential target for OS treatment. Graphical Abstract |
| Related Links | https://josr-online.biomedcentral.com/counter/pdf/10.1186/s13018-023-04520-y.pdf |
| Ending Page | 13 |
| Page Count | 13 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s13018-023-04520-y |
| Journal | Journal of Orthopaedic Surgery and Research |
| Issue Number | 1 |
| Volume Number | 19 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-01-13 |
| Access Restriction | Open |
| Subject Keyword | Orthopedics Surgical Orthopedics Osteosarcoma circ_0000376 miR-577 HK2 LDHA |
| Content Type | Text |
| Resource Type | Article |
| Subject | Surgery Orthopedics and Sports Medicine |
| Journal Impact Factor | 2.8/2023 |
| 5-Year Journal Impact Factor | 3/2023 |
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