MicroRNA-125 modulates radioresistance through targeting p21 in cervical cancer

Abstract

Cervical cancer (CC) is one of the most common cancers diagnosed in women worldwide, and it is estimated that ∼500,000 new patients are diagnosed with cervical cancer annually and that ∼270,000 deaths occur each year. Patients with cervical cancer are treated with different radiotherapy schedules, either alone or with adjuvant chemotherapy. Unfortunately, nearly 50% of all patients with cervical cancer do not respond to standard treatment due to tumor radioresistance. In this scenario, several microRNAs (miRNAs) have been associated with the acquisition of the radioresistance phenotype. The aim of the present study was to evaluate the possible role of miR-125a in the acquisition of radioresistance in cervical cancer. The expression of miR-125a was assessed by means of RT-qPCR in 30 cervical cancer samples from patients receiving standard treatment and 3 induced radioresistant cervical cancer cell lines. In addition, we employed miR-125a mimics and inhibitors to evaluate its function in the induction of radioresistance. We showed that miR-125a was downregulated in patients with cervical cancer who did not respond to standard treatment. Concordantly, radioresistant SiHa, CaSki and HeLa cell lines had low levels of miR-125a with respect to the sensitive cell lines. Finally, we demonstrated that overexpression of miR-125a sensitized cervical cancer cells to radiation therapy through the downregulation of CDKN1A. Our data corroborate previously published studies in which it was demonstrated that miRNAs could play a role in the regulation of the process of radioresistance. Additionally, we showed that overexpression of miR-125a could be used as a radioresistance biomarker in patients with cervical cancer.