AI Article Synopsis
- Hepatocellular carcinoma (HCC) is difficult to treat due to high rates of recurrence and radiation resistance, and this study explores the role of a circular RNA called circEYA3 in this context.
- The research found that circEYA3 decreases HCC cell sensitivity to radiation by interacting with the protein IGF2BP2, which stabilizes the DTX3L mRNA and helps the cells resist radiation-induced damage.
- These findings suggest that circEYA3 could be used as a potential biomarker or target for improving treatment outcomes in HCC patients undergoing radiation therapy.
Article Abstract
Background: Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under I and X-ray irradiation conditions.
Methods: CircEYA3 was identified by RNA-seq in patients with HCC before and after I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model.
Results: CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells.
Conclusions: Our findings demonstrate that circEYA3 increases the radioresistance of HCC to I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for I brachytherapy or external radiotherapy in HCC.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693171 | PMC |
| http://dx.doi.org/10.1186/s12935-023-03168-2 | DOI Listing |
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