CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR-637 and up-regulating SOX10
Chen Jin1, Jie Zhao1, Zhi-Ping Zhang1
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Gliomas are the most common type of primary brain tumors. CircRNA ephrin type-B receptor 4 (circEPHB4) is a circular RNA derived from the receptor tyrosine kinase EPHB4. However, the clinical significance and the specific roles of circEPHB4 in gliomas and glioma cancer stem cells (CSC) have not been studied. Here, we found that circEPHB4 (hsa_circ_0081519) and SOX10 were up-regulated and microRNA (miR)-637 was down-regulated in glioma tissues and cell lines. Consistently, circEPHB4 was positively correlated with SOX10 but negatively correlated with miR-637. The altered expressions of these molecules were independently associated with overall survival of patients. CircEPHB4 up-regulated SOX10 and Nestin by directly sponging miR-637, thereby stimulating stemness, proliferation and glycolysis of glioma cells. Functionally, silencing circEPHB4 or increasing miR-637 levels in glioma cells was sufficient to inhibit xenograft growth in vivo. In conclusion, the circEPHB4/miR-637/SOX10/Nestin axis plays a central role in controlling stem properties, self-renewal and glycolysis of glioma cells and predicts the overall survival of glioma patients. Targeting this axis might provide a therapeutic strategy for malignant gliomas.
Insights
Circular RNA circEPHB4 promotes glioma progression by sponging miR-637, upregulating SOX10 and Nestin. Targeting the circEPHB4/miR-637/SOX10 axis may offer a novel therapeutic strategy for malignant gliomas.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gliomas are primary brain tumors with limited therapeutic options.
- Cancer stem cells (CSCs) drive tumor growth and recurrence in gliomas.
- The role of circular RNA ephrin type-B receptor 4 (circEPHB4) in glioma and CSCs remains unelucidated.
Purpose of the Study:
- To investigate the clinical significance and functional role of circEPHB4 in gliomas.
- To explore the molecular mechanisms underlying circEPHB4's function in glioma and CSCs.
- To assess the potential of the circEPHB4/miR-637/SOX10 axis as a therapeutic target.
Main Methods:
- Quantitative real-time PCR to assess circEPHB4, miR-637, and SOX10 expression.
- Correlation analysis between molecule expression and patient survival.
- In vitro experiments including cell transfection and Western blotting to study molecular interactions.
- In vivo xenograft models to evaluate the therapeutic efficacy of targeting the circEPHB4 axis.
Main Results:
- circEPHB4 and SOX10 were upregulated, while miR-637 was downregulated in glioma tissues and cell lines.
- circEPHB4 expression positively correlated with SOX10 and negatively with miR-637.
- circEPHB4 promoted glioma stemness, proliferation, and glycolysis by sponging miR-637 and upregulating SOX10 and Nestin.
- Silencing circEPHB4 or enhancing miR-637 inhibited tumor growth in vivo.
Conclusions:
- The circEPHB4/miR-637/SOX10/Nestin axis is crucial for glioma stemness, self-renewal, and glycolysis.
- This axis serves as a potential biomarker for overall survival in glioma patients.
- Targeting this axis presents a promising therapeutic strategy for malignant gliomas.
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