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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 0010117 promotes aggressive glioblastoma behavior by regulating the miRNA-6779-5p/SPEN axis
Xuanyong Yang1, Yue Liu1, Xinhui Zhou2
1Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, China.
Abstract:
Noncoding RNAs (ncRNAs) play important roles in cancer biology, providing potential targets for cancer intervention. As a new class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified in cell development and function, and certain types of pathological responses contribute to cancer progression, including glioblastoma. However, the potential mechanisms underlying the relationship between circRNAs and glioblastoma progression are still largely unknown. Methods: The expression and roles of circular RNA 0010117 (circ-0010117) were examined in vitro and in vivo. Quantitative RT‒PCR and western blotting were used to measure the expression of circRNA, miRNA, each gene, or related proteins. Cell biology experiments were performed to detect the biological function of circ-0010117 in glioblastoma cell lines. Moreover, bioinformatics analysis, luciferase reporter assays, and functional complementation analysis were carried out to investigate the target genes. Tumorigenesis was also evaluated by xenografting cells into nude mice. In this study, we found that circ-0010117 is downregulated in glioblastoma compared with corresponding paratumoural tissues. Subsequently, we observed that circ-0010117 can regulate aggressiveness in glioblastoma cells through miR-6779-5p. Furthermore, SPEN was verified as a direct target of miR-6779-5p and contributes to the circ-0010117 regulatory network. In addition, we identified that overexpression of circ-0010117 can suppress tumorigenesis in nude mice. Our findings indicate that circular RNA 0010117 promotes the aggressive behavior of glioblastoma by regulating the miRNA-6779-5p/SPEN axis. Our results provide a rationale for the use of circ-0010117 as a novel potential therapeutic target in glioblastoma.
Insights
Circular RNA 0010117 (circ-0010117) is downregulated in glioblastoma and suppresses tumor growth. This circular RNA regulates glioblastoma aggressiveness via the miR-6779-5p/SPEN axis, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Noncoding RNAs (ncRNAs) are crucial in cancer biology.
- Circular RNAs (circRNAs) are a novel class of ncRNAs implicated in glioblastoma progression.
- Mechanisms linking circRNAs to glioblastoma remain largely unknown.
Purpose of the Study:
- To investigate the expression and function of circRNA 0010117 (circ-0010117) in glioblastoma.
- To elucidate the molecular mechanisms by which circ-0010117 influences glioblastoma aggressiveness.
- To evaluate circ-0010117 as a potential therapeutic target for glioblastoma.
Main Methods:
- Quantitative RT-PCR and Western blotting for expression analysis.
- In vitro cell-based assays and in vivo xenograft models for functional studies.
- Bioinformatics, luciferase reporter assays, and functional complementation to identify targets.
Main Results:
- circ-0010117 was found to be downregulated in glioblastoma tissues.
- circ-0010117 suppressed glioblastoma cell aggressiveness by regulating miR-6779-5p.
- SPEN was identified as a direct target of miR-6779-5p, forming the circ-0010117/miR-6779-5p/SPEN axis.
- Overexpression of circ-0010117 inhibited tumor growth in vivo.
Conclusions:
- circ-0010117 suppresses glioblastoma progression by modulating the miR-6779-5p/SPEN pathway.
- circ-0010117 represents a promising novel therapeutic target for glioblastoma treatment.
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