miR-21-5p inhibitor enhances the radiosensitivity of human cervical cancer cells via blocking CPEB3-mediated CDK1/cyclin B pathway

Currently, radiotherapy remains the standard treatment for human cervical cancer (CC), while approximately 30 % of patients are still non-responsive to radiotherapy, leading to radioresistance. Therefore, it is urgent to discover a novel therapeutic target/biomarker for the radiosensitivity of cervical cancer, and it will be beneficial to clinical guiding significance for individualized treatment of cervical cancer. Herein, the correlation of miR-21-5p and clinicopathological features, clinical efficacy, radiotherapy sensitivity and survival were investigated, and our results showed that miR-21-5p is positively correlated to radio-sensitivity in patients with CC. Furthermore, we found that inhibition of miR-21-5p significantly suppressed the growth of HeLa and SiHa cells, and induced early apoptosis. Meanwhile, miR-21-5p inhibitor caused an arrest cell cycle at G2/M phase. Of note, the miR-21-5p inhibitor significantly enhanced the efficacy of radiation in a dose and timing-dependent manner in human cervical cancer cells. Mechanistically, our results demonstrated that miR-21-5p inhibitior directly up-regulated CPEB3 and further suppressed CDK1/cyclin B pathway. The blockage of CDK1/cyclin B is responsible to the suppression of miR-21-5p and arresting cell cycle at G2/M. Taken together, miR-21-5p can serve as a potential predictor/biomarker for radioresistance and poor prognosis of CC patients. Our results suggested that miR-21-5p inhibitor effectively restored the radio-sensitivity of CC cells through blocking CPEB3-mediated CDK1/Cyclin B pathway.