MiR-7-5p is a key factor that controls radioresistance via intracellular Fe2+ content in clinically relevant radioresistant cells

Kazuo Tomita, Manabu Fukumoto, Katsuhiko Itoh, Yoshikazu Kuwahara, Kento Igarashi, Taisuke Nagasawa, Masatoshi Suzuki, Akihiro Kurimasa, Tomoaki Sato

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

MicroRNA (miRNA) is a non-coding RNA involved in regulating both cancer gene promotion and suppression. We investigated the role of miRNA in inducing radiation resistance in cancer cell lines using clinically relevant radioresistant (CRR) cells. Analysis using miRNA arrays and qPCR revealed that miR-7-5p is highly expressed in all examined CRR cells. Additionally, CRR cells lose their radioresistance when daily irradiation is interrupted for over 6 months. MiR-7-5p expression is reduced in these cells, and treating CRR cells with a miR-7-5p inhibitor leads to a loss of resistance to irradiation. Conversely, overexpression of miR-7-5p in CRR cells using a miR-7-5p mimic shows further resistance to radiation. Overexpression of miR-7-5p in parent cells also results in resistance to radiation. These results indicate that miR-7-5p may control radioresistance in various cancer cells at the clinically relevant dose of irradiation. Furthermore, miR-7-5p downregulates mitoferrin and reduces Fe2+, which influences ferroptosis. Our findings have great potential not only for examining radiation resistance prior to treatment but also for providing new therapeutic agents for treatment-resistant cancers.

Original languageEnglish
Pages (from-to)712-718
Number of pages7
JournalBiochemical and biophysical research communications
Volume518
Issue number4
DOIs
Publication statusPublished - 2019 Oct 22

Keywords

  • CRR cells
  • Radiation resistance
  • microRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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