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Knockdown of circ-TTBK2 Inhibits Glioma Progression by Regulating miR-1283 and CHD1
Chengchen Han1, Shuwei Wang1, Hongwei Wang1
1Department of Neurosurgery, The Sixth Medical Center of PLA General Hospital, Beijing 100048, People's Republic of China.
Background:
Dysregulated circular RNAs (circRNAs) are involved in the development of glioma. This paper aims to analyze the role and mechanism of circRNA tau tubulin kinase 2 (circ-TTBK2) in glioma progression.
Methods:
The glioma samples and normal brain tissues were collected. The levels of circ-TTBK2, microRNA-1283 (miR-1283) and chromodomain helicase DNA-binding protein 1 (CHD1) were examined via quantitative reverse transcription polymerase chain reaction or Western blot. Cell proliferation, migration, invasion and glycolysis were determined via 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, transwell assay, Western blot, glucose and lactate assay kits. The target relationship was analyzed via dual-luciferase reporter assay. The xenograft model was established using U251 cells.
Results:
circ-TTBK2 expression was increased in glioma tissues and cells. circ-TTBK2 knockdown suppressed glioma cell proliferation, migration, invasion and glycolysis. circ-TTBK2 was a sponge for miR-1283, and knockdown of miR-1283 reversed the effect of circ-TTBK2 silence on glioma progression. CHD1 was targeted via miR-1283, and miR-1283 repressed glioma cell proliferation, migration, invasion and glycolysis via decreasing CHD1. Knockdown of circ-TTBK2-reduced CHD1 expression by mediating miR-1283. Silence of circ-TTBK2 reduced xenograft tumor growth.
Conclusion:
Down-regulation of circ-TTBK2 suppressed glioma development by regulating miR-1283 and CHD1, providing a new mechanism for understanding glioma pathogenesis.
Insights
Down-regulating circRNA tau tubulin kinase 2 (circ-TTBK2) inhibits glioma progression by affecting microRNA-1283 (miR-1283) and chromodomain helicase DNA-binding protein 1 (CHD1). This provides a new mechanism for understanding glioma pathogenesis.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Dysregulated circular RNAs (circRNAs) are implicated in glioma development.
- Circular RNA tau tubulin kinase 2 (circ-TTBK2) role in glioma progression requires elucidation.
Purpose of the Study:
- To investigate the role and mechanism of circ-TTBK2 in glioma progression.
- To analyze the regulatory network involving circ-TTBK2, miR-1283, and CHD1 in glioma.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction and Western blot to assess molecule levels.
- Cell-based assays (proliferation, migration, invasion, glycolysis) and dual-luciferase reporter assay to determine function and interactions.
- Xenograft model in mice to evaluate in vivo tumor growth.
Main Results:
- circ-TTBK2 expression is upregulated in glioma tissues and cells.
- circ-TTBK2 knockdown suppresses glioma cell proliferation, migration, invasion, and glycolysis.
- circ-TTBK2 acts as a sponge for miR-1283, which targets CHD1, ultimately inhibiting glioma progression.
Conclusions:
- Downregulation of circ-TTBK2 suppresses glioma development by regulating the miR-1283/CHD1 axis.
- This study reveals a novel mechanism contributing to glioma pathogenesis.
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