MicroRNA expression profiles in human breast cancer cells after multifraction and single-dose radiation treatment

  • Chung Man Leung
  • , Ting Wen Chen
  • , Sung Chou Li
  • , Meng Ru Ho
  • , Ling Yueh Hu
  • , Wen Shan Liu
  • , Tony T. Wu
  • , Ping Chi Hsu
  • , Hong Tai Chang
  • , Kuo Wang Tsai*
  • *Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

39 Scopus citations

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that contribute to modulating signaling pathways after radiation exposure and have emerged as a potential therapeutic target or biomarker in the radiation response of cancer. Exposing breast cancer cells to single-dose (SD) or multifractionated (MF) radiation may affect the cells differently. However, the roles of miRNAs in breast cancer cells after the response to SD or MF is not thoroughly understood. Therefore, the purpose of the present study was to comprehensively investigate the response of miRNAs in MDA-MB-361 by using various radiation exposing protocols. Our results revealed that only a small fraction of miRNAs exhibiting differential expressions (>1.5.fold) was identified after MDA-MB-361 cells were exposed to SD (10.Gy) or MF radiation (2.Gy.x.5.MF). In addition, we observed that several miRNAs in the MDA-MB-361 cells frequently exhibited differential responses to various types of radiation treatment. Among these miRNAs, the expression levels of an oncogenic miR-17-92 cluster increased following SD radiation treatment. Conversely, miR-19a-3p, miR-20a-5p, and miR-19b-3p expressions were inhibited by >1.5-fold in the following MF treatment. Further analysis of the miR-17-92 cluster expression levels revealed that miR-17, miR-18a, miR-19a/b and miR-20a were significantly overexpressed and miR-92a was downregulated in breast cancer. Functional annotation demonstrated that target genes of the miR-17-92 cluster were predominantly involved in the regulation of radiation-associated signal pathways such as mitogen-activated protein kinase (MAPK), ErbB, p53, Wnt, transforming growth factor-β (TGF-β), mTOR signaling pathways and cell cycles with an FDR <0.05. Overall, the results of the present study revealed distinct differences in the response of miRNAs to SD and MF radiation exposure, and these radiation-associated miRNAs may contribute to radiosensitivity and can be used as biomarkers for radiotherapy.

Original languageEnglish
Pages (from-to)2147-2156
Number of pages10
JournalOncology Reports
Volume31
Issue number5
DOIs
StatePublished - 05 2014
Externally publishedYes

Keywords

  • Breast cancer
  • MiR-17-92 cluster
  • MicroRNA
  • Next-generation sequencing
  • Pathway enrichment analysis
  • Radiation
  • TCGA

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