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CircPUM1 Knockdown Confers Radiosensitivity in Oral Squamous Cell Carcinoma by Regulating the miR-580/STAT3 Pathway
Linghui Jia1,2, Pengcheng Huang1,3, Tingting Lin4
1Fujian Key Laboratory of Oral Diseases, Fujian Provincial Engineering Research Center of Oral Biomaterial of Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
Abstract:
Background: CircPUM1 acts as an oncogene in a variety of tumors, and there is no related research on oral squamous cell carcinoma. This study aimed to evaluate the clinical significance of CircPUM1 in oral squamous cell carcinoma radiotherapy. Methods: Radio-resistant cell lines were established by increasing the X-ray dose. Analysis of CircPUM1 expression in oral squamous cell carcinoma was carried out using bioinformatics tools. Cell proliferation was analyzed with CCK-8 and colony formation. Protein and gene expressions were detected by Western blotting and qPCR. RNA interference inhibits endogenous gene expression. A luciferase reporter system and immunoprecipitation were used to validate the target of CircPUM1. Result: CircPUM1 was highly expressed in OSCC. The higher the expression level of CircPUM1 in OSCC, the worse the clinical features and prognosis. Knockdown of CircPUM1 enhances the sensitivity of OSCC cells to X-rays, and expression of exogenous CircPUM1 makes OSCC cells acquire radiation resistance. The absence of CircPUM1 blocked the cells in the G0/G1 phase and triggered apoptosis. The prediction of mir-580-binding site, luciferase reporter system, and immunoprecipitation confirmed that mir-580 is the binding site of CircPUM1. In addition, STAT3 was predicted and confirmed as the binding site of mir-580. Overexpression of STAT3 partially attenuated the radiosensitivity of OSCC cells to knockdown of CircPUM1. Conclusion: CircPUM1 has the oncogene expression profile in oral squamous cell carcinoma; patients with high expression of CircPUM1 have less benefit from radiotherapy and need more frequent follow-up. In addition, CircPUM1 may be a potential therapeutic target for oral squamous cell carcinoma. The CircPUM1/mir-580/STAT3 axis has a certain effect on the radiosensitivity of OSCC. These results suggest that patients with low expression of CircPUM1 may gain more benefits.
Insights
Circular PUM1 (CircPUM1) is highly expressed in oral squamous cell carcinoma (OSCC), correlating with poor prognosis and reduced radiotherapy benefit. Targeting CircPUM1 may improve treatment outcomes for OSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy Research
Background:
- Circular PUM1 (CircPUM1) is an oncogene implicated in various cancers.
- Its role in oral squamous cell carcinoma (OSCC) and its impact on radiotherapy remain unexplored.
Purpose of the Study:
- To investigate the clinical significance and mechanistic role of CircPUM1 in oral squamous cell carcinoma (OSCC) radiotherapy.
- To explore the potential of CircPUM1 as a therapeutic target for improving radiotherapy efficacy in OSCC.
Main Methods:
- Establishment of radio-resistant OSCC cell lines.
- Bioinformatic analysis of CircPUM1 expression.
- Cell proliferation assays (CCK-8, colony formation).
- Western blotting, qPCR, RNA interference, luciferase reporter assays, and immunoprecipitation.
Main Results:
- CircPUM1 is highly expressed in OSCC, associated with adverse clinical features and poorer prognosis.
- CircPUM1 knockdown increases OSCC radiosensitivity; its overexpression confers resistance.
- CircPUM1 regulates cell cycle (G0/G1 arrest) and apoptosis.
- The CircPUM1/mir-580/STAT3 axis influences OSCC radiosensitivity.
Conclusions:
- CircPUM1 exhibits oncogenic properties in OSCC and predicts reduced benefit from radiotherapy.
- CircPUM1 is a potential therapeutic target for OSCC.
- The CircPUM1/mir-580/STAT3 pathway is crucial for OSCC radiosensitivity, suggesting low CircPUM1 expression may lead to better treatment outcomes.
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