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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
LncRNA DDX11-AS1 Exerts Oncogenic Roles in Glioma Through Regulating miR-499b-5p/RWDD4 Axis
Yanyan Zheng1, Jing Xie2, Xiaomin Xu1
1Department of Neurology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou 325000, People's Republic of China.
Background:
Long noncoding RNAs (lncRNA) exert essential functions during tumorigenesis. However, how lncRNAs participate in glioma development remains poorly researched. This study aimed to determine how DDX11-AS1 affects glioma progression.
Methods:
Gene expression was analyzed by qRT-PCR. Survival rate curve was plotted in 56 glioma patients. Loss-of-function assays were performed to analyze proliferation, migration, and invasion through CCK8, colony formation, and transwell assays. Luciferase assay and RNA pulldown assays were conducted to illustrate the underlying molecular mechanism.
Results:
DDX11-AS1 expression was upregulated in glioma tissues and cells. DDX11-AS1 overexpression was linked with poor prognostic value. DDX11-AS1 knockdown suppressed proliferation, migration, and invasion while inducing apoptosis. DDX11-AS1 interacted with miR-499b-5p to eliminate it, leading to upregulation of RWDD4 expression. RWDD4 was upregulated in glioma while miR-499b-5p was downregulated.
Conclusion:
DDX11-AS1 upregulation promotes glioma progression through acting as a competing endogenous RNA for miR-499b-5p to upregulate RWDD4.
Insights
The long noncoding RNA DDX11-AS1 promotes glioma progression by interacting with miR-499b-5p, leading to increased RWDD4 expression. This finding offers potential therapeutic targets for glioma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis.
- The specific involvement of lncRNAs in glioma development is not well understood.
Purpose of the Study:
- To investigate the role of DDX11-AS1 in glioma progression.
- To elucidate the molecular mechanism by which DDX11-AS1 influences glioma.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for gene expression analysis.
- Patient survival analysis and in vitro functional assays (CCK8, colony formation, transwell).
- Luciferase and RNA pulldown assays to determine molecular interactions.
Main Results:
- DDX11-AS1 expression is significantly upregulated in glioma tissues and cells.
- High DDX11-AS1 expression correlates with a poor prognosis in glioma patients.
- Knockdown of DDX11-AS1 inhibits glioma cell proliferation, migration, and invasion, while promoting apoptosis.
- DDX11-AS1 acts as a competing endogenous RNA (ceRNA) by sponging miR-499b-5p, leading to the upregulation of its target gene, RWDD4.
- RWDD4 is upregulated, and miR-499b-5p is downregulated in glioma.
Conclusions:
- Upregulation of DDX11-AS1 promotes glioma progression.
- The DDX11-AS1/miR-499b-5p/RWDD4 axis is a key mechanism in glioma development.
- DDX11-AS1 represents a potential therapeutic target for glioma.
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