Sugiyama Hikoto, Kikuchi Megumi, Chiba Mitsuru, Hosokawa Yoichiro, Monzen Satoru
Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan.
Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan.
Mol Med Rep. 2025 Oct;32(4). doi: 10.3892/mmr.2025.13645. Epub 2025 Aug 8.
Patients with acute myeloid leukemia (AML) generally receive total body irradiation at a high‑dose rate for the ablation of bone marrow cells, including AML cells. However, in rare cases, radioresistant AML cells appear, interfering with the therapeutic effect. HL60 cells were used to model a radioresistant leukemia cell line that emerged from repeated radiation exposure (Res‑HL60). Notably, the mechanism through which microRNA (miRNA/miR) expression influences radioresistance in this model is unclear. In the current study, the expression profile of the miRNAs included in the small RNAs in Res‑HL60 was analyzed using an miRNA microarray. A total of 1,187 miRNAs were retained for analysis after normalization. Among them, 27 miRNAs (10 upregulated and 17 downregulated in Res‑HL60 cells compared with wild‑type‑HL60 cells) exhibited P<0.05 and fold change >1.5 or <0.66. Furthermore, the expression levels of five miRNAs were validated by reverse transcription‑quantitative PCR: miR‑146a‑5p (upregulated), and miR‑30c‑1‑3p, miR‑671‑5p, miR‑610 and miR‑3675‑5p (downregulated). To investigate the target mRNAs of these five miRNAs, OmicsNet (ver. 2.0) was used. A total of 27 mRNAs were identified as targets of these multiple miRNAs. Furthermore, Reactome analysis revealed enrichment in the following processes 'Cell cycle, Mitotic' (R‑HAS‑69278), 'Apoptosis' (R‑HAS‑109581) and 'Immune system' (R‑HAS‑168256), suggesting that these miRNAs regulate genes involved in these pathways. These findings indicated that the altered expression of five specific microRNAs in radioresistant AML cells may be associated with radioresistant conditions through the modulation of mRNA expression.
急性髓系白血病（AML）患者通常接受高剂量率的全身照射，以消融包括AML细胞在内的骨髓细胞。然而，在罕见情况下，会出现抗辐射的AML细胞，干扰治疗效果。HL60细胞被用于模拟因反复辐射暴露而产生的抗辐射白血病细胞系（Res-HL60）。值得注意的是，在该模型中，微小RNA（miRNA/miR）表达影响抗辐射能力的机制尚不清楚。在当前研究中，使用miRNA微阵列分析了Res-HL60中小RNA中包含的miRNA的表达谱。标准化后共保留1187个miRNA用于分析。其中，27个miRNA（与野生型HL60细胞相比，Res-HL60细胞中有10个上调，17个下调）表现出P<0.05且倍数变化>1.5或<0.66。此外，通过逆转录定量PCR验证了5个miRNA的表达水平：miR-146a-5p（上调），以及miR-30c-1-3p、miR-671-5p、miR-610和miR-3675-5p（下调）。为了研究这5个miRNA的靶mRNA，使用了OmicsNet（版本2.0）。共鉴定出27个mRNA为这些多个miRNA的靶标。此外，Reactome分析显示在以下过程中富集：“细胞周期，有丝分裂”（R-HAS-69278）、“凋亡”（R-HAS-109581）和“免疫系统”（R-HAS-168256），表明这些miRNA调节参与这些途径的基因。这些发现表明，抗辐射AML细胞中5种特定微小RNA的表达改变可能通过调节mRNA表达与抗辐射状态相关。
