Department of Applied Pharmacology Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima, 890-8544, Japan.
Department of Molecular Pathology, Tokyo Medical University, 6-1-1, Shinjuku, Shinjuku-ku, Tokyo, 1608402, Japan.
Biochem Biophys Res Commun. 2019 Oct 22;518(4):712-718. doi: 10.1016/j.bbrc.2019.08.117. Epub 2019 Aug 28.
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 Fe, 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.
微 RNA（miRNA）是一种非编码 RNA，参与调控癌症基因的促进和抑制。我们使用临床相关的耐辐射（CRR）细胞研究了 miRNA 在诱导癌细胞系辐射抗性中的作用。miRNA 阵列和 qPCR 分析显示，miR-7-5p 在所有检查的 CRR 细胞中均高度表达。此外，当每日照射中断超过 6 个月时，CRR 细胞会失去其辐射抗性。这些细胞中 miR-7-5p 的表达减少，用 miR-7-5p 抑制剂处理 CRR 细胞会导致对辐射的抗性丧失。相反，用 miR-7-5p 模拟物在 CRR 细胞中过表达 miR-7-5p 会进一步增强对辐射的抗性。亲本细胞中 miR-7-5p 的过表达也会导致对辐射的抗性。这些结果表明，miR-7-5p 可能在临床相关辐射剂量下控制各种癌细胞的辐射抗性。此外，miR-7-5p 下调 mitoferrin 并减少 Fe，这影响铁死亡。我们的研究结果不仅有可能在治疗前检查辐射抗性，而且有可能为治疗耐药性癌症提供新的治疗剂。
