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Abstract

Radiotherapy represents the most effective non-surgical modality in cancer treatment. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, and are involved in many biological processes and diseases. To identify miRNAs that influence the radiation response, we performed miRNA array analysis using MCF7 cells at 2, 8, and 24 h post irradiation. We demonstrated that miR-770-5p is a novel radiation-inducible miRNA. When miR-770-5p was overexpressed, relative cell number was reduced due to increased apoptosis in MCF7 and A549 cells. Transcriptomic and bioinformatic analyses revealed that PDZ-binding kinase (PBK) might be a possible target of miR-770-5p for regulation of radiosensitivity. PBK regulation mediated by direct targeting of miR-770-5p was demonstrated using luciferase reporter assays along with wild-type and mutant PBK-3'untranslated region constructs. Radiation sensitivity increased and decreased in miR-770-5p- and anti-miR-770-5p-transfected cells, respectively. Consistent with this result, transfection of short interfering RNA against PBK inhibited cell proliferation, while ectopic expression of PBK restored cell survival from miR-770-5p-induced cell death. In addition, miR-770-5p suppressed tumor growth, and miR-770-5p and PBK levels were inversely correlated in xenograft model mice. Altogether, these data demonstrated that miR-770-5p might be a useful therapeutic target miRNA that sensitizes tumors to radiation via negative regulation of PBK.

Author information

Lee HC1,2, Her NG3, Kang D1,2, Jung SH1,2, Shin J4, Lee M5, Bae IH6, Kim YN7, Park HJ2,4, Ko YG3, Lee JS1,2.​

1 Department of Molecular Medicine, Inha University College of Medicine, Incheon, Korea.

2 Hypoxia-related Disease Research Center, Inha University College of Medicine, Incheon, Korea.

3 Division of Life Sciences, Korea University, Seoul, Korea.

4 Department of Microbiology, Inha University College of Medicine, Incheon, Korea.

5 Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

6 Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

7 Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Korea.