Yaqin Wu1, Jian Huang1, Hanzi Xu2, Zhen Gong3. 1. Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 21000, China. 2. Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 21000, China. Electronic address: xuhanzi2010@163.com. 3. Department of Gynecology, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 21000, China. Electronic address: peacemind@126.com.
Abstract
BACKGROUND: Radioresistance is a challenge in the treatment of cervical cancer. Recent studies have reported that microRNAs (miRNAs) mediate radiotherapy resistance and play a vital role in the occurrence and development of cancer. The aim of this study was to investigate whether the expression of miR-15a-3p was correlated with radiosensitivity in cervical cancer. METHODS: Quantitative real-time PCR experiment was performed to detect the expression of miR-15a-3p in cervical cancer tissues and cells lines. Then, the effect of miR-15a-3p on proliferation in cervical cancer cells radiation-induced were determined by using CCK-8, clonogenic formation and EdU assays. In addition, the TUNEL, flow cytometry analysis and western blotting assays were conducted to evaluate radiation-induced cells apoptosis. A dual-luciferase reporter assay was used to test the target. In addition, tumor xenograft experiment was conducted to test tumor growth in vivo. RESULTS: In this study, miR-15a-3p was downregulated in cervical cancer tissues and cells lines, however, the expression of miR-15a-3p significantly increased exposed to radiation. Moreover, over-expression of miR-15a-3p inhibited cells proliferation and enhanced cells apoptosis radiation-induced. Further, TPD52 was identified as a direct target of miR-15a-3p. Inhibition of TPD52 could suppress cells proliferation and induce cells apoptosis. Tumor xenograft experiments indicated that over-expression of miR-15a-3p could increase sensitivity to radiation therapy by targeting TPD52. CONCLUSION: In conclusion, our findings suggested that miR-15a-3p enhanced radiosensitivity in cervical cancer by targeting tumor protein D52, suggesting that miR-15a-3p may be a potential therapeutic target for cervical cancer patients.
BACKGROUND: Radioresistance is a challenge in the treatment of cervical cancer. Recent studies have reported that microRNAs (miRNAs) mediate radiotherapy resistance and play a vital role in the occurrence and development of cancer. The aim of this study was to investigate whether the expression of miR-15a-3p was correlated with radiosensitivity in cervical cancer. METHODS: Quantitative real-time PCR experiment was performed to detect the expression of miR-15a-3p in cervical cancer tissues and cells lines. Then, the effect of miR-15a-3p on proliferation in cervical cancer cells radiation-induced were determined by using CCK-8, clonogenic formation and EdU assays. In addition, the TUNEL, flow cytometry analysis and western blotting assays were conducted to evaluate radiation-induced cells apoptosis. A dual-luciferase reporter assay was used to test the target. In addition, tumor xenograft experiment was conducted to test tumor growth in vivo. RESULTS: In this study, miR-15a-3p was downregulated in cervical cancer tissues and cells lines, however, the expression of miR-15a-3p significantly increased exposed to radiation. Moreover, over-expression of miR-15a-3p inhibited cells proliferation and enhanced cells apoptosis radiation-induced. Further, TPD52 was identified as a direct target of miR-15a-3p. Inhibition of TPD52 could suppress cells proliferation and induce cells apoptosis. Tumor xenograft experiments indicated that over-expression of miR-15a-3p could increase sensitivity to radiation therapy by targeting TPD52. CONCLUSION: In conclusion, our findings suggested that miR-15a-3p enhanced radiosensitivity in cervical cancer by targeting tumor protein D52, suggesting that miR-15a-3p may be a potential therapeutic target for cervical cancerpatients.