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CircRNA NALCN acts as an miR-493-3p sponge to regulate PTEN expression and inhibit glioma progression
Yi Liu1, Simin Chen2, Gang Peng1
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background:
An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in the regulation of tumor progression. Therefore, we explored the expression characteristics, function, and related mechanism of the newly identified circNALCN in glioma.
Methods:
RNA sequencing was used to analyze the expression profiles of circRNAs in brain tissue from five glioma cases and four normal controls. Quantitative real-time polymerase chain reaction was implemented to examine the levels of circNALCN, miR-493-3p, and phosphatase and tensin homolog (PTEN). Cell counting kit 8 assays were performed to analyze cell proliferation, and cell migration was assessed by the wound healing test and Transwell assay. Dual-luciferase reporter, fluorescence in situ hybridization, and RNA pulldown assays were performed to confirm the role of circNALCN as an miR-493-3p sponge, weakening the inhibitory effect of miR-493-3p on target PTEN expression.
Results:
The downregulated expression of circNALCN was observed in both glioma tissues and cell lines. CircNALCN expression was negatively correlated with World Health Organization grade and overall survival in patients with glioma. Functionally, the overexpression of circNALCN significantly inhibited the proliferation and migration of glioma cells, whereas miR-493-3p mimics counteracted these effects. The mechanistic analysis demonstrated that circNALCN acted as a competing endogenous RNA for miR-493-3p to relieve the repressive effects of miR-493-3p on its target, PTEN, suppressing glioma tumorigenesis.
Conclusions:
CircNALCN inhibits the progression of glioma through the miR-493-3p/PTEN axis, providing a developable biomarker and therapeutic target for glioma patients.
Insights
Circular RNAs (circRNAs) like circNALCN are crucial in cancer. This study found circNALCN inhibits glioma progression by regulating the miR-493-3p/PTEN pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in tumor progression.
- The specific functions and mechanisms of the novel circNALCN in glioma remain largely unexplored.
Purpose of the Study:
- To investigate the expression patterns of circNALCN in glioma.
- To elucidate the functional role and underlying molecular mechanism of circNALCN in glioma progression.
Main Methods:
- RNA sequencing to analyze circRNA expression profiles in glioma tissues and controls.
- Quantitative real-time PCR to measure circNALCN, miR-493-3p, and PTEN levels.
- Cell proliferation and migration assays (CCK-8, wound healing, Transwell) to assess functional impact.
- Dual-luciferase reporter, FISH, and RNA pulldown assays to confirm the circNALCN-miR-493-3p-PTEN interaction.
Main Results:
- CircNALCN expression was significantly downregulated in glioma tissues and cell lines.
- Lower circNALCN levels correlated with higher World Health Organization grade and poorer overall survival.
- Overexpression of circNALCN suppressed glioma cell proliferation and migration.
- Mechanistically, circNALCN functions as a sponge for miR-493-3p, thereby relieving miR-493-3p-mediated repression of PTEN.
Conclusions:
- CircNALCN inhibits glioma progression via the miR-493-3p/PTEN axis.
- CircNALCN represents a promising biomarker and therapeutic target for glioma.
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