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CircPOLR2A Promotes Proliferation and Impedes Apoptosis of Glioblastoma Multiforme Cells by Up-regulating POU3F2 to
Zide Chen1, Qicong Mai1, Qi Wang1
1Department of Interventional Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
Abstract:
Glioblastoma multiforme (GBM) is the most common cancer in nervous system around the world. Little advancement has been achieved in promoting prognosis of GBM patients. Circular RNAs (circRNAs) are suggested as crucial effectors in modulating GBM development. Hsa_circRNA_092437 (circPOLR2A), an up-regulated circRNA in GBM cells, has not been studied yet. In this study, RT-qPCR and western blot assays were applied to detect RNA and protein levels. Cell proliferation and apoptosis were analyzed via functional assays. Subcellular fractionation assay was carried out to determine circPOLR2A distribution in cells. Bioinformatics analysis and mechanism assays were done for detecting relationships among different factors. Rescue assays were performed to confirm validity of circPOLR2A/SOX9 axis. According to experimental results, circPOLR2A was up-regulated in GBM cells and promoted GBM cell proliferation while inhibiting GBM cell apoptosis. CircPOLR2A mainly existed in cell cytoplasm and sponged miR-2113 to positively regulate POU3F2 expression. POU3F2 activated the transcription of SOX9 through interacting with SOX9 promoter (1-500). Rescue assays validated that circPOLR2A influenced GBM cell proliferation and apoptosis via SOX9. To conclude, circPOLR2A enhanced the transcription of SOX9 through miR-2113/POU3F2 axis, thus exacerbating GBM cells growth.
Insights
Circular RNA hsa_circRNA_092437 (circPOLR2A) promotes glioblastoma multiforme (GBM) growth by increasing SOX9 transcription. This study reveals circPOLR2A as a potential therapeutic target for GBM.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is the most prevalent nervous system cancer globally, with limited therapeutic advancements.
- Circular RNAs (circRNAs) are implicated in GBM development, but the specific role of hsa_circRNA_092437 (circPOLR2A) remains uninvestigated.
Purpose of the Study:
- To investigate the role and mechanism of circPOLR2A in glioblastoma multiforme (GBM) progression.
- To elucidate the regulatory pathway involving circPOLR2A, miR-2113, POU3F2, and SOX9 in GBM cells.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blot assays to measure RNA and protein expression.
- Functional assays (proliferation, apoptosis) and subcellular fractionation to assess cellular effects and localization.
- Bioinformatics analysis, mechanism assays, and rescue experiments to determine molecular interactions and functional validation.
Main Results:
- circPOLR2A was significantly upregulated in GBM cells, promoting proliferation and inhibiting apoptosis.
- circPOLR2A, primarily located in the cytoplasm, acts as a molecular sponge for miR-2113, upregulating POU3F2.
- POU3F2 enhances SOX9 transcription by interacting with its promoter, a process validated by rescue assays showing circPOLR2A influences GBM via the SOX9 pathway.
Conclusions:
- circPOLR2A promotes GBM cell proliferation and survival by enhancing SOX9 transcription through the miR-2113/POU3F2 axis.
- circPOLR2A represents a potential therapeutic target for glioblastoma treatment, offering a novel avenue for intervention.
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