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Identification of insulin-like growth factor 2 mRNA-binding protein 3 as a radioresistance factor in squamous
K Yoshino1, S Motoyama, S Koyota
1Department of Surgery, Akita University Graduate School of Medicine, Akita, Japan.
Abstract:
Identification of reliable markers of radiosensitivity and the key molecules that donate susceptibility to anticancer treatments to esophageal cancer cells would be highly desirable. We found that the mRNA expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was higher in radioresistant TE-5 and TE-9 cells than in radiosensitive TE-12 cloneA1 cells. Conversely, knocking down expression of IGF2BP3 mRNA in TE-5 and TE-9 cells using small interfering RNA significantly enhanced their radiosensitivity. Furthermore, patients with squamous cell esophageal cancers strongly expressing IGF2BP3 tended to respond poorly to chemoradiation. These data suggest that IGF2BP3 may be a key marker of radiosensitivity that diminishes the susceptibility of squamous cell esophageal cancer cells to radiotherapy. IGF2BP3 may, thus, be a useful target for improving radiotherapy for patients with esophageal squamous cell carcinoma.
Insights
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is highly expressed in radioresistant esophageal cancer cells. Lowering IGF2BP3 levels can improve radiosensitivity, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy Research
Background:
- Identifying markers for radiosensitivity in esophageal cancer is crucial for treatment optimization.
- Understanding molecular mechanisms of radioresistance can lead to targeted therapies.
Purpose of the Study:
- To investigate the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in esophageal cancer radiosensitivity.
- To evaluate IGF2BP3 as a potential predictive marker and therapeutic target for esophageal squamous cell carcinoma.
Main Methods:
- Quantitative analysis of IGF2BP3 mRNA expression in esophageal cancer cell lines with varying radiosensitivity.
- In vitro experiments using small interfering RNA (siRNA) to knockdown IGF2BP3 expression.
- Correlation analysis of IGF2BP3 expression with patient response to chemoradiation.
Main Results:
- IGF2BP3 mRNA expression was significantly higher in radioresistant esophageal cancer cell lines (TE-5, TE-9) compared to radiosensitive ones (TE-12 cloneA1).
- Knockdown of IGF2BP3 using siRNA markedly increased the radiosensitivity of TE-5 and TE-9 cells.
- High IGF2BP3 expression in patients with squamous cell esophageal carcinoma correlated with poor response to chemoradiation.
Conclusions:
- IGF2BP3 is a key molecule associated with radioresistance in esophageal squamous cell carcinoma.
- IGF2BP3 expression levels can serve as a predictive marker for radiotherapy response.
- Targeting IGF2BP3 presents a promising strategy for enhancing the efficacy of radiotherapy in esophageal cancer treatment.
