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Biochem Biophys Res Commun. 2019 Oct 22;518(4):712-718. doi: 10.1016/j.bbrc.2019.08.117. Epub 2019 Aug 28.

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

Author information

1
Department of Applied Pharmacology Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan.
2
Department of Molecular Pathology, Tokyo Medical University, 6-1-1, Shinjuku, Shinjuku-ku, Tokyo, 1608402, Japan.
3
Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
4
Department of Applied Pharmacology Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan; Department of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, miyagino-ku, Sendai, Miyagi, 983-8536, Japan.
5
Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku Sendai, Miyagi, 980-8575, Japan.
6
Department of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, miyagino-ku, Sendai, Miyagi, 983-8536, Japan.
7
Department of Applied Pharmacology Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan. Electronic address: tomsato@dent.kagoshima-u.ac.jp.

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.

KEYWORDS:

CRR cells; Radiation resistance; microRNA

PMID:
31472959
DOI:
10.1016/j.bbrc.2019.08.117

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