title: MicroRNA-145 sensitizes cervical cancer cells to low-dose irradiation by downregulating OCT4 expression.
abstract: Poor elucidation of the mechanisms involved in regulating the radiosensitivity of cancers prevents the extensive application of low-dose radiotherapy in clinical settings. The present study was conducted to investigate the role of microRNA-145 (miR-145) in the modulation of cervical cancer cell radiosensitivity, as well as to identify the underlying target of miR-145 during this process. Cervical cancer tera cells were initially exposed to doses of radiation between 1 and 6 Gy before the assessments of the cell viability and apoptosis rate. Irradiation at dose of 1 Gy was screened as optimum dose and used in subsequent experiments. A dual luciferase reporter assay was performed to demonstrate that octamer-binding transcription factor 4 (OCT4) is a target of miR-145 in cervical cancer. Consequently, OCT4 was suggested to be a target of miR-145, as a dual luciferase vector that was ligated to a fragment corresponding to the predicted target site of miR-145 in OCT4 3'-UTR showed an 83% reduction in fluorescence. Following exposure to 1 Gy irradiation, tera cells transfected with miR-145 mimics, which showed downregulation of OCT4 and cyclin D1, had lower cell viability and cell migration rate and higher apoptosis rate compared to non-transfected cells. However, the co-transfection of miR-145 mimics and OCT4 expression vector restored OCT4 and cyclin D1 expression levels and made no significant difference in terms of cell viability, cell migration rate and apoptosis rate. The present results indicate that miR-145 increases the radiosensitivity of cervical cancer cells by silencing OCT4, that cyclin D1 is putatively under the positive regulation of OCT4 and mediates miR-145 function.
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Oncology, The Second People's Hospital, Changsha, Hunan 410000, P.R. China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
keywords: cervical cancer; low-dose irradiation; microRNA-145; octamer-binding transcription factor 4; radiosensitivity