Integrative genomic and proteomic analyses identifies glycerol-3-phosphate acyltransferase as a target of low-dose ionizing radiation in EBV infected-B cells

Yoko Tabe, Yasuhito Hatanaka, Mayumi Nakashiro, Kazumasa Sekihara, Shinichi Yamamoto, Hiromichi Matsushita, Saiko Kazuno, Tsutomu Fujimura, Takako Ikegami, Keita Nakanaga, Hirotaka Matsumoto, Takashi Ueno, Junken Aoki, Takehiko Yokomizo, Marina Konopleva, Michael Andreeff, Takashi Miida, Kazuhisa Iwabuchi, Keisuke Sasai

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: We sought to gain a better understanding of the low-dose ionizing radiation (LDIR)-induced molecular changes in transformed pre-malignant cells in their microenvironment.Materials and methods: The cellular response to LDIR was compared and contrasted using immortalized human Epstein-Barr virus-infected B-cells (EBV-B) in mono-culture, co-culture with human bone marrow derived stromal cells (MSC), or under the LDIR-induced bystander effect. The resulting alterations in protein and gene expression (including microRNA, miRNA) were evaluated by isobaric tags for relative and absolute quantification (iTRAQ) proteomics assay, western blot, cDNA array and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively.Results: The miRNAs let7a, miR-15b, miR-16, and miR-21, and a lipid metabolic miRNA hub miR-23b, were upregulated after LDIR exposure in the mono-cultured EBV-B cells, but were downregulated in EBV-B cells co-irradiated with MSC. A lipid biosynthesis enzyme glycerol-3-phosphate acyltransferase, the common target of these miRNA, was downregulated at the level of protein and mRNA expression in the LDIR-exposed, mono-cultured EBV-B cells and upregulated MSC co-cultured EBV-B cells.Conclusions: These results suggest a putative miRNA regulatory mechanism controlling the LDIR-induced stress response, and illustrate that LDIR exposure, and the cells microenvironment, can affect specific gene expression, both directly and indirectly, resulting in altered protein expression.

Original languageEnglish
Pages (from-to)24-34
Number of pages11
JournalInternational Journal of Radiation Biology
Volume92
Issue number1
DOIs
Publication statusPublished - 2016 Jan 2

Keywords

  • Epstein-Barr virus-infected B-cells (EBV-B)
  • Low-dose ionizing radiation (LDIR)
  • glycerol-3-phosphate acyltransferase (GPAM)
  • isobaric tags for relative and absolute quantification (iTRAQ)
  • microRNA (miRNA)

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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    Tabe, Y., Hatanaka, Y., Nakashiro, M., Sekihara, K., Yamamoto, S., Matsushita, H., Kazuno, S., Fujimura, T., Ikegami, T., Nakanaga, K., Matsumoto, H., Ueno, T., Aoki, J., Yokomizo, T., Konopleva, M., Andreeff, M., Miida, T., Iwabuchi, K., & Sasai, K. (2016). Integrative genomic and proteomic analyses identifies glycerol-3-phosphate acyltransferase as a target of low-dose ionizing radiation in EBV infected-B cells. International Journal of Radiation Biology, 92(1), 24-34. https://doi.org/10.3109/09553002.2015.1106021