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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Circular RNA circHECTD1 facilitates glioma progression by regulating the miR-296-3p/SLC10A7 axis
Chenlong Li1, Yan Liu2, Zhonghua Lv1
1Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
Abstract:
Glioma is the most common type of primary brain tumor. Treatment options for recurrent gliomas include surgery, chemotherapy, and radiation therapy, but the clinical outcome is usually limited. In recent years, circular RNAs have been found to play a vital role in several human cancers. Gene Expression Omnibus database was utilized to verify the differentially expressed circRNAs. Then we detected that the expression of circular RNA circHECTD1 was significantly increased. The expression and function of circHECDT1 has not yet been reported in glioma. Then we confirmed that the level of circHECTD1 was significantly increased both in glioma tissues and cell lines, which is negatively correlated with the overall survival of patients. Knockdown of circHECTD1 inhibited proliferation and invasion in vitro, and also reduced the growth of tumor and prolonged the prognosis in vivo. Knockdown of circHECTD1 significantly elevated the miR-296-3p expression in LN229 and T98G cells. Luciferase reports and RNA immunoprecipitation data indicated that miR-296-3p was a direct target of circHECTD1 and that the miR-296-3p expression negatively regulated SLC10A7. Rescue experiments showed that the overexpression of SLC10A7 could impede the effects of circHECTD1 silencing on the proliferation and invasion of glioma cells. In this study, we identified that circHECTD1 regulates SLC10A7 by interacting with miR-296-3p in glioma cells. In conclusion, this study investigated a novel biomarker panel consisting of the circHECTD1/miR-296-3p/SLC10A7 axis, which is critical for glioma tumorigenesis and invasiveness and may represent a novel therapeutic target for intervening in glioma progression.
Insights
Circular RNA circHECTD1 is upregulated in glioma and promotes tumor growth and invasion by regulating the miR-296-3p/SLC10A7 axis. Targeting this axis offers a potential therapeutic strategy for glioma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma is a common primary brain tumor with limited treatment outcomes for recurrent cases.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in human cancers.
- The specific role of circHECTD1 in glioma remains largely unexplored.
Purpose of the Study:
- To investigate the expression and function of circHECTD1 in glioma.
- To elucidate the molecular mechanism underlying circHECTD1's role in glioma progression.
- To identify potential therapeutic targets for glioma treatment.
Main Methods:
- Utilized the Gene Expression Omnibus database to identify differentially expressed circRNAs.
- Quantified circHECTD1 expression in glioma tissues and cell lines.
- Performed in vitro and in vivo experiments to assess the functional impact of circHECTD1 knockdown.
- Conducted luciferase reporter assays and RNA immunoprecipitation to validate molecular interactions.
- Performed rescue experiments to confirm the regulatory pathway.
Main Results:
- CircHECTD1 expression was significantly elevated in glioma tissues and cell lines, correlating with poorer patient survival.
- Knockdown of circHECTD1 suppressed glioma cell proliferation and invasion in vitro and reduced tumor growth in vivo.
- CircHECTD1 directly targets miR-296-3p, which in turn negatively regulates SLC10A7.
- Overexpression of SLC10A7 partially rescued the inhibitory effects of circHECTD1 silencing.
Conclusions:
- Identified a novel circHECTD1/miR-296-3p/SLC10A7 axis critical for glioma tumorigenesis and invasiveness.
- CircHECTD1 acts as an oncogenic circRNA in glioma by sponging miR-296-3p and upregulating SLC10A7.
- The circHECTD1/miR-296-3p/SLC10A7 pathway represents a promising therapeutic target for glioma intervention.
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