MicroRNA-218 enhances the radiosensitivity of human cervical cancer via promoting radiation induced apoptosis.
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 (R(2)=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.
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.
Wang
W
Yuan
3. Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Shandong Province, 250117, China.
Han
H
Xiaoyun
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.
Qiu
Q
Haifeng
5. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, 510060, China.
Li
L
Jing
6. Department of Radiation Oncology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
Hu
H
Weixu
2. Department of Obstetrics and Gynecology, the Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Jiangsu Province, 214062, China.
Dong
D
Ruofan
2. Department of Obstetrics and Gynecology, the Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Jiangsu Province, 214062, China.
Yu
Y
Jinjin
1. Department of Obstetrics and Gynecology, First Affiliated Hospital of Soochow University, Jiangsu Province, 215006, China.
Shen
S
Zongji
D000328:Adult; D017209:Apoptosis / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011836:Radiation Tolerance / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D023041:Xenograft Model Antitumor Assays
C547471:MIRN218 microRNA, human; D035683:MicroRNAs
cervical cancer; miR-218; radiotherapy; sensitivity.