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CircHECTD1 Regulates Cell Proliferation and Migration by the miR-320-5p/SLC2A1 Axis in Glioblastoma Multiform
Wen Li1, Shanshan Wang1, Boquan Shan1
1Department of Anatomy and Neurobiology, Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Abstract:
Glioblastoma multiform (GBM) is the most common and malignant primary brain cancer in adults, and thus, novel potential therapeutic targets for diagnosis and treatment are urgently needed. Circular RNAs (circRNAs) are a class of widespread and diverse endogenous RNAs that have been suggested as potential critical mediators during progression of various tumors. In this study, we investigated the involvement of circHECTD1 in GBM progression. CircHECTD1 Lentivirus, miR-320-5p mimic, and SLC2A1 Lentivirus were transduced into cancer cells independently or together. circHECTD1, miR-320-5p, and SLC2A1 level were detected by qRT-PCR. Western blot and qRT-PCR were applied to measure the expression of SLC2A1, CyclinD1, CDK2, and PCNA. Flow cytometry, EdU, colony formation, Transwell and wound-healing assays were conducted to assess cell proliferation and migration. Luciferase reporter assays were performed to determine the effect of miR-320-5p on circHECTD1 or SLC2A1. Xenograft experiments were implemented to evaluate tumor growth in vivo. CircHECTD1 expression led to the promotion of proliferation and migration of GBM cells. In addition, circHECTD1 acted as a ceRNA to interact with miR-320-5p, which targeted the solute carrier family 2 member 1 (SLC2A1). In vivo experiments also revealed that circHECTD1 promoted tumor growth. Collectively, our findings showed that the circHECTD1-miR-320-5p-SLC2A1 regulatory pathway promoted the progression of GBM, suggesting that circHECTD1 may be a therapeutic target for GBM.
Insights
Circular RNAs (circRNAs) like circHECTD1 promote glioblastoma (GBM) growth by regulating the miR-320-5p/SLC2A1 pathway. This pathway offers a potential therapeutic target for this aggressive brain cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is a highly aggressive primary brain cancer with limited treatment options.
- Circular RNAs (circRNAs) are emerging as key regulators in tumor progression and potential therapeutic targets.
- Understanding the role of specific circRNAs in GBM is crucial for developing novel strategies.
Purpose of the Study:
- To investigate the role of circHECTD1 in the progression of glioblastoma.
- To elucidate the molecular mechanism involving circHECTD1, miR-320-5p, and SLC2A1 in GBM.
- To evaluate circHECTD1 as a potential therapeutic target for GBM.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blot to detect RNA and protein expression.
- Cellular assays including flow cytometry, EdU, colony formation, Transwell, and wound-healing assays to assess proliferation and migration.
- Luciferase reporter assays and in vivo xenograft experiments to confirm interactions and evaluate tumor growth.
Main Results:
- circHECTD1 expression significantly promoted GBM cell proliferation and migration.
- circHECTD1 functions as a competing endogenous RNA (ceRNA) by sponging miR-320-5p.
- miR-320-5p directly targets solute carrier family 2 member 1 (SLC2A1), and circHECTD1 upregulates SLC2A1 expression.
Conclusions:
- The circHECTD1-miR-320-5p-SLC2A1 axis plays a critical role in promoting GBM progression.
- circHECTD1 enhances GBM cell proliferation and migration through this regulatory pathway.
- circHECTD1 represents a promising therapeutic target for glioblastoma treatment.
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