AI Article Synopsis
- Endometrial cancer (EC) is a common gynecological cancer, but patients often develop resistance to chemotherapy, making treatment challenging.
- Researchers discovered that the protein RNF8 is overexpressed in EC cells that are resistant to commonly used drugs like cisplatin and doxorubicin, suggesting it plays a role in this resistance.
- By eliminating RNF8 in resistant EC cells, the study showed increased sensitivity to chemotherapy and reduced DNA repair efficiency, indicating that targeting RNF8 could enhance the effectiveness of treatment for EC patients.
Article Abstract
Endometrial cancer (EC) is one of the most frequent gynecological malignancy worldwide. However, resistance to chemotherapy remains one of the major difficulties in the treatment of EC. Thus, there is an urgent requirement to understand mechanisms of chemoresistance and identify novel regimens for patients with EC. We found that protein and mRNA expression levels of RNF8 were significantly increased in both cisplatin and doxorubicin resistant EC cells. Cell survival assay showed that RNF deficiency significantly enhanced the sensitivity of resistant EC cells to cisplatin and doxorubicin (P < 0.01). In addition, chemoresistant EC cells exhibited increased NHEJ efficiency. Knockout of RNF8 in chemoresistant EC cells significantly reduced NHEJ efficiency and prolonged Ku80 retention on DSB. Moreover, cisplatin resistant AN3CA xenograft showed that RNF8 deficiency overcame cisplatin resistance. Our in vitro and in vivo assays provide evidence for RNF8, which is a NHEJ factor, serving as a promising, novel target in EC chemotherapy.
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| http://dx.doi.org/10.1016/j.bbrc.2021.01.046 | DOI Listing |
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