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Cyclin G2 Inhibits Oral Squamous Cell Carcinoma Growth and Metastasis by Binding to IGFBP3 and Regulating the
Danning Wang1, Jinlan Gao1, Chenyang Zhao1
1The Research Center for Medical Genomics, Key Laboratory of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang, China.
Abstract:
The cell cycle protein cyclin G2 is considered a tumor suppressor. However, its regulatory effects and potential mechanisms in oral cancers are not well understood. This study aimed to investigate the effect of cyclin G2 on oral squamous cell carcinoma (OSCC). The data from 80 patients with OSCC were utilized to predict the abnormal expression of cyclin G2. The proliferation and metastasis were determined by a cell counting Kit-8 assay, flow cytometry, a wound-healing assay, and a cell invasion assay. The expression of key proteins and genes associated with the cyclin G2 signaling pathways was determined by western blotting and real-time PCR, respectively. The orthotopic nude mice model was established by a mouth injection of SCC9 cells overexpressing cyclin G2. We showed that the low level of cyclin G2 in OSCC, which is negatively correlated with clinical staging, was a negative prognostic factor for the disease. We also found that cyclin G2 inhibited the proliferation, metastasis, and blocked the cell cycle at G1/S of OSCC cells, suggesting that cyclin G2 has an inhibitory effect in OSCC. Mechanistically, cyclin G2 inhibited the growth and metastasis of OSCC by binding to insulin-like growth factor binding protein 3 (IGFBP3) and regulating the focal adhesion kinase (FAK) -SRC-STAT signal transduction pathway. Cyclin G2 competed with integrin to bind to IGFBP3; the binding between integrin and IGFBP3 was reduced after cyclin G2 overexpression, thereby inhibiting the phosphorylation of FAK and SRC. These results showed that cyclin G2 inhibited the progression of OSCC by interacting with IGFBP3 and that it may be a new target for OSCC treatment.
Insights
Cyclin G2 acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). Overexpression of cyclin G2 inhibits OSCC proliferation and metastasis by interacting with IGFBP3, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cyclin G2 is a cell cycle protein with known tumor suppressor roles.
- Its specific functions and regulatory mechanisms in oral cancers remain largely unelucidated.
- Oral squamous cell carcinoma (OSCC) represents a significant global health challenge.
Purpose of the Study:
- To investigate the role and underlying mechanisms of cyclin G2 in oral squamous cell carcinoma.
- To determine the prognostic significance of cyclin G2 expression in OSCC patients.
Main Methods:
- Analysis of cyclin G2 expression in 80 OSCC patient samples.
- In vitro assays including cell counting Kit-8, flow cytometry, wound-healing, and cell invasion assays.
- Western blotting and real-time PCR to assess protein and gene expression.
- Orthotopic nude mice model for in vivo validation.
Main Results:
- Low cyclin G2 expression in OSCC is linked to advanced clinical staging and poorer prognosis.
- Overexpression of cyclin G2 significantly inhibited OSCC cell proliferation, metastasis, and induced G1/S cell cycle arrest.
- Cyclin G2 was found to inhibit OSCC progression by binding to insulin-like growth factor binding protein 3 (IGFBP3) and modulating the FAK-SRC-STAT pathway.
Conclusions:
- Cyclin G2 exhibits a tumor-suppressive role in oral squamous cell carcinoma.
- The interaction between cyclin G2 and IGFBP3 is crucial for inhibiting OSCC growth and metastasis.
- Cyclin G2 represents a promising novel therapeutic target for oral cancer treatment.
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