title: A specific miRNA signature promotes radioresistance of human cervical cancer cells.
abstract: BACKGROUND
  The mechanisms responsible for cervical cancer radioresistance are still largely unexplored. The present study aimed to identify miRNAs associated with radioresistance of cervical cancer cells.
  
  
  METHODS
  The radioresistant cervical cancer cell variants were established by repeated selection with irradiation. The miRNA profiles of radioresistant cells and their corresponding controls were analyzed and compared using microarray. Differentially expressed miRNAs were confirmed by quantitative real-time PCR. Cervical cancer cells were transfected with miRNA-specific mimics or inhibitors. Radiosensitivity of cervical cancer cells were determined using colony-forming assay.
  
  
  RESULTS
  Among the differentially expressed miRNAs, 20 miRNAs showed the similar pattern of alteration (14 miRNAs were overexpressed whilst 6 were suppressed) in all three radioresistant cervical cancer cell variants compared to their controls. A miRNA signature consisting of 4 miRNAs (miR-630, miR-1246, miR-1290 and miR-3138) exhibited more than 5 folds of increase in radioresistant cells. Subsequent analysis revealed that these four miRNAs could be up-regulated in cervical cancer cells by radiation treatment in both time-dependent and dose-dependent manners. Ectopic expression of each of these 4 miRNAs can dramatically increase the survival fraction of irradiated cervical cancer cells. Moreover, inhibition of miR-630, one miRNA of the specific signature, could reverse radioresistance of cervical cancer cells.
  
  
  CONCLUSIONS
  The present study indicated that miRNA is involved in radioresistance of human cervical cancer cells and that a specific miRNA signature consisting of miR-630, miR-1246, miR-1290 and miR-3138 could promote radioresistance of cervical cancer cells.
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.|State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|School of Aerospace Medicine, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Osteology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Ren
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, 169 Changle Western Road, Xi'an, Shaanxi 710032, China.
authors.forename: Junye
authors.initials: J
authors.lastname: Liu