1. Department of Obstetrics and Gynecology, First Affiliated Hospital of Soochow University, Jiangsu Province, 215006, China.
2. Department of Obstetrics and Gynecology, the Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Jiangsu Province, 214062, China.
3. Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Shandong Province, 250117, China.
4. Department of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiaotong University, Shanghai, 200030, China.
5. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, 510060, China.
6. Department of Radiation Oncology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
* The two authors contribute equally to this work.
We previously reported frequent loss of microRNA-218 (miR-218) in cervical cancer, which was associated with tumor progression and poor prognosis. As microRNAs were found invovled in the regulation of radiosensitivity in various human cancers, we therefore aim to investigate the effects of miR-218 on radiosensitivity of cervical cancer in the present study. The clonogenic survival assay demonstrated that loss of miR-218 could predict radioresistance in the primary cervical cancer cells (R2=0.6516, P<0.001). In vitro, abundant miR-218 increased the radiosensitivity in cervical cancer cells (P<0.001 for HeLa, P=0.009 for SiHa, P=0.016 for C33A and P=0.01 for CaSki). Upregulation of miR-218 significantly enhanced the radiation-induced apoptosis, which was further enhanced by the combination of miR-218 overexpression and radiation In xenograft growth assay, combination of miR-218 overexpression and radiation notably induced cellular apoptosis and suppressed tumor growth. In conclusion, we demonstrated that miR-218 resensitized cervical cancer cells to radiation via promoting cellular apoptosis. Moreover, we proved that miR-218 as a potent predictor of radiosensitivity in cervical cancer, especially for those patients with loss of miR-218.
Keywords: cervical cancer, miR-218, radiotherapy, sensitivity.