Radiation-inducible miR-770-5p sensitizes tumors to radiation through direct targeting of PDZ-binding kinase

Hyung Chul Lee, Nam Gu Her, Donghee Kang, Seung Hee Jung, Jinwook Shin, Minyoung Lee, In Hwa Bae, Young Nyun Kim, Heon Joo Park, Young-Gyu Ko, Jae Seon Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)e2693
JournalCell death & disease
Volume8
Issue number3
DOIs
Publication statusPublished - 2017 Mar 23

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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    Lee, H. C., Her, N. G., Kang, D., Jung, S. H., Shin, J., Lee, M., Bae, I. H., Kim, Y. N., Park, H. J., Ko, Y-G., & Lee, J. S. (2017). Radiation-inducible miR-770-5p sensitizes tumors to radiation through direct targeting of PDZ-binding kinase. Cell death & disease, 8(3), e2693. https://doi.org/10.1038/cddis.2017.116