Abstract / Summary
Cervical cancer is the 4th most common malignancy in women. Radiotherapy (RT) plays an essential role in cervical cancer treatments, and this study reports the role of REV7 in cervical cancer RT. Results showed that loss of REV7 contributed to increased the radiosensitivity of cervical cancer both in vitro and in vivo. Further molecular biology experiments demonstrated REV7-silence enhanced apoptosis, aggravated radiation-induced ROS, and accelerated ferroptosis after RT. Mass spectrometry was used to explore the candidate substrates of REV7 involved in the regulation of cervical cancer cell radiosensitivity. Mass spectrometry and co-immunoprecipitation confirmed that SFXN1 is a candidate substrate for REV7. The expression of SFXN1 was negatively regulated by REV7 in HeLa cells. Consistently, REV7 deficiency aggravated ferroptosis by increasing SFXN1. Our findings revealed that REV7 conferred radioresistance of cervical cancer cell by downregulating SFXN1 expression. Moreover, REV7 physically interacts with SFXN1 and negatively regulates its expression through an ubiquitin-dependent proteasomal degradation pathway. In conclusion, REV7 depletion induce ferroptosis and enhance the radiosensitivity of cervical cancer cells in an SFXN1-dependent manner, indicating that targeting REV7 is a plausible candidate that possesses potential for the radiosensitization of cervical cancer.