Micro RNA-218 Enhanced The Radio-sensitivity In Cervical Cancer Through Promoting Cellular Apoptosis

Part I Micro RNA-218 was downregulated in the sera of cervical cancer patients and associated with tumor invasionBackground Micro RNA-218(mi R-218) was demonstrated to be a tumor-suppressor factor in many cancers, but its expression and biological functions had not been reported in cervical cancer. In this study, we investigated the expression level of micro RNA-218 in the cervical cancer patients’ sera and the correlations between micro RNA-218 and cervical patients’ clinico-pathological characteristics.Methods In this study, we detected the expression of micro RNA-218 in 90 cervical cancer patients’ sera and 50 normal age-matched women’ sera by quantitative transcriptive PCR. Then we collected the clinical data and analyzed it by statistical software.Results We found that micro RNA-218 was reduced significantly in the cervical cancer patients’ sera compared with the normal control,(P< 0.001). Moreover, we found that reduced micro RNA-218 was related with advanced tumor stage, the subtype of adenocarcinoma, positive lymphatic node metastasis and so on(P<0.001, P<0.001 and P<0.001, respectively).Conclusions Micro RNA-218 in cervical cancer patients’ sera was significantly downregulated and the degree was associated with tumor invasion.Part II Micro RNA-218 increased the radio-sensitivity of cervical cancer through enhancing cellular apoptosisBackgrounds We previously demonstrated that frequent downregulation ofMicroRNA-218 micro RNA-218 in cervical cancer patients’ sera, which was associated with tumor invasion and poor prognosis. Herein, we aimed to explore its effects on the cellular radio-sensitivity of cervical cancer.Methods we detected the expression of micro RNA-218 in a group of 35 cervical cancer and 20 non-cancerous cervical tissues by real-time PCR. Then we used clonogenic survival analysis and flow cytometry to investigate the effects of micro RNA-218 overexpression on cellular proliferation and apoptosis in cervical cancer. Primary cultured cervical cancer cells were used to detect the radiosensitivity when micro RNA-218 was changed.Results In vitro,we found that upregulation of micro RNA-218 increased cellular radiosensitivity in all the four human cervical cancer cell lines. Elevated micro RNA-218 also significantly increased the cell apoptosis, which was further enhanced by combining with radiation and micro RNA-218 overexpression. In vivo, we discovered that the therapy combined with micro RNA-218 overexpression and radiation significantly suppressed tumor growth and promoted cellular apoptosis. Primary culture using human cervical cancer samples also showed loss of micro RNA-218 could predict resistance to radiotherapy(R2=0.6516, P<0.001).Conclusions Overexpressioned micro RNA-218 could enhance cellular apoptosis and increase the radio-sensitivity of cervical cancer. Moreover, we demonstrated that micro RNA-218 could serve as a marker to predict the radio-sensitivity in cervical cancer patients, which need to be verified in our further project.