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Circ-EGFR Functions as an Inhibitory Factor in the Malignant Progression of Glioma by Regulating the miR-183-5p/TUSC2
Qingdong Guo1, Jun Guo2, Wei Liu1
1Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.127, Changle West Road, Xincheng District, Xi'an, 710032, China.
Abstract:
Circular RNAs (circRNAs) have pivotal functions in regulating diverse biological processes of human tumors, including glioma. Herein, a novel circRNA epidermal growth factor receptor (circ-EGFR, hsa_circ_0080223) was researched in glioma. The molecular expression levels were analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and colony formation assays were conducted to assess cell proliferation. Apoptosis was analyzed using flow cytometry. Cell migration and invasion were examined via transwell assay. Interaction relations between targets were verified using dual-luciferase reporter assay. Tumor Suppressor Candidate 2 (TUSC2) protein expression was examined by Western blot. In vivo experiment was performed by establishing xenograft model in mice. The qRT-PCR showed the downregulation of circ-EGFR and TUSC2 but the upregulation of microRNA-183-5p (miR-183-5p) in glioma samples. In vitro assays revealed that circ-EGFR overexpression induced the repression of cell proliferation, migration, and invasion but the promotion of apoptosis. Circ-EGFR was identified as a sponge of miR-183-5p and circ-EGFR-mediated glioma progression inhibition was abolished by miR-183-5p downregulation. Additionally, miR-183-5p targeted TUSC2 and miR-183-5p inhibitor impeded the development of glioma by upregulating the expression of TUSC2. Furthermore, circ-EGFR could regulate the TUSC2 level by sponging miR-183-5p. Glioma growth in vivo was also reduced by circ-EGFR via targeting the miR-183-5p/TUSC2 axis. Altogether, our results suggested that circ-EGFR inhibited the malignant progression of glioma by regulating the levels of miR-183-5p and TUSC2. Circ-EGFR may be a useful therapeutic target to antagonize the glioma progression.
Insights
Circular RNA epidermal growth factor receptor (circ-EGFR) acts as a tumor suppressor in glioma by inhibiting cell proliferation, migration, and invasion. It functions by regulating miR-183-5p and TUSC2 levels, offering a potential therapeutic target for glioma.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Circular RNAs (circRNAs) play critical roles in regulating biological processes within human tumors, including glioma.
- The specific role of circRNA epidermal growth factor receptor (circ-EGFR) in glioma pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the expression and function of circ-EGFR in glioma.
- To explore the molecular mechanism underlying circ-EGFR's role in glioma progression, focusing on its interactions with microRNA-183-5p (miR-183-5p) and Tumor Suppressor Candidate 2 (TUSC2).
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression analysis.
- Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays for in vitro functional studies.
- Dual-luciferase reporter assay for target interaction verification and Western blot for protein expression analysis.
- In vivo xenograft model in mice to assess tumor growth.
Main Results:
- Circ-EGFR and TUSC2 were downregulated, while miR-183-5p was upregulated in glioma samples.
- Overexpression of circ-EGFR suppressed glioma cell proliferation, migration, and invasion, while promoting apoptosis in vitro.
- Circ-EGFR acted as a sponge for miR-183-5p, and this axis, along with TUSC2 regulation, inhibited glioma progression both in vitro and in vivo.
Conclusions:
- Circ-EGFR functions as a tumor suppressor in glioma by inhibiting malignant progression through the regulation of the miR-183-5p/TUSC2 axis.
- Circ-EGFR represents a promising therapeutic target for counteracting glioma progression.
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