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Hypoxia-associated circDENND2A promotes glioma aggressiveness by sponging miR-625-5p
Hui Su1,2, Defei Zou1,2, Yikun Sun3
11Department of Neurosurgery, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, People's Republic of China.
Background:
As a newfound type of non-coding RNA, circular RNAs (circRNAs) are involved in various physiological and pathological processes via regulation of gene expression. Increasing evidence shows that aberrantly expressed circRNAs play a crucial role in the initiation and progression of many tumors. However, the functions of different circRNAs in gliomas remain elusive.
Methods:
The levels of circRNAs, miRNAs, and mRNAs were quantified by qPCR. The interaction between circDENND2A and miR-625-5p was determined by luciferase reporter and pull-down assays. The migratory and invasive capabilities of glioma cells were examined by wound healing and Transwell assays. Immunohistochemistry was performed to analyze the HIF1α level in glioma tissues.
Results:
We predicted circDENND2A (has_circ_0002142) to be a hypoxia-responsive circRNA in glioma via a bioinformatic analysis. We found that hypoxia induced the expression of circDENND2A, which promoted migration and invasion of glioma cells. To understand the behaviors of circDENND2A in glioma, we studied the putative miRNAs targeted by circDENND2A and identified circDENND2A as an efficient sponge of miR-625-5p in glioma cells. Phenotype experiments verified that circDENND2A was required for the hypoxia-induced migration and invasion of glioma cells and that this occurred by sponging of miR-625-5p. Notably, glioma tissues overexpressing HIF1α exhibited a high expression of circDENND2A as well as a low expression of miR-625-5p. circDENND2A was negatively correlated with miR-625-5p.
Conclusion:
circDENND2A is required for the hypoxia-induced malignancy of glioma cells and functions by sponging miR-625-5p.
Insights
Circular RNAs (circRNAs) like circDENND2A promote glioma cell migration and invasion. circDENND2A acts as a sponge for miR-625-5p, contributing to hypoxia-induced tumor malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are key regulators of gene expression involved in various cellular processes.
- Aberrant circRNA expression is implicated in tumor development and progression.
- The specific roles of circRNAs in glioma pathogenesis remain largely unexplored.
Purpose of the Study:
- To investigate the function of circDENND2A in glioma.
- To elucidate the mechanism by which circDENND2A influences glioma cell behavior.
- To determine the relationship between circDENND2A, miR-625-5p, and hypoxia in glioma.
Main Methods:
- Quantitative real-time PCR (qPCR) for circRNA, miRNA, and mRNA levels.
- Luciferase reporter and pull-down assays to confirm circRNA-miRNA interaction.
- Wound healing and Transwell assays to assess cell migration and invasion.
- Immunohistochemistry to analyze HIF1α expression in glioma tissues.
Main Results:
- Hypoxia induces circDENND2A expression in glioma cells, promoting their migration and invasion.
- circDENND2A functions as a molecular sponge for miR-625-5p in glioma.
- Knockdown of circDENND2A inhibits hypoxia-induced glioma cell migration and invasion.
- High circDENND2A and low miR-625-5p expression correlate with HIF1α overexpression in glioma tissues.
Conclusions:
- circDENND2A is essential for hypoxia-induced glioma cell malignancy.
- circDENND2A promotes glioma progression by sponging miR-625-5p.
- circDENND2A represents a potential therapeutic target in glioma.
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