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

## TL;DR

This study shows that inhibiting miR-21-5p can make cervical cancer cells more responsive to radiation therapy by blocking a specific cell cycle pathway.

## Contribution

The novel finding is that miR-21-5p inhibition enhances radiosensitivity in cervical cancer cells via the CPEB3-mediated CDK1/cyclin B pathway.

## Key findings

- miR-21-5p is positively correlated with radio-sensitivity in cervical cancer patients.
- miR-21-5p inhibitor arrests the cell cycle at G2/M phase and induces apoptosis in cervical cancer cells.
- Blocking the CPEB3/CDK1/cyclin B pathway via miR-21-5p inhibition enhances radio-sensitivity in cervical cancer cells.

## Abstract

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.

Image 1

•MiR-21-5p is positively correlated to radio-sensitivity in patients with cervical cancer.•MiR-21-5p inhibitor arrested cell cycle at G2/M phase and induced cellular apoptosis.•MiR-21-5p inhibitor enhances the radio-sensitivity of cervical cancer cells via blocking CPEB3/CDK1/Cyclin B pathway.

MiR-21-5p is positively correlated to radio-sensitivity in patients with cervical cancer.

MiR-21-5p inhibitor arrested cell cycle at G2/M phase and induced cellular apoptosis.

MiR-21-5p inhibitor enhances the radio-sensitivity of cervical cancer cells via blocking CPEB3/CDK1/Cyclin B pathway.