Relationship between specific microRNA expression and radioresistant conditions in HL60 acute myeloid leukemia cells

HL60急性髓系白血病细胞中特定microRNA表达与放射抗性之间的关系

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Abstract

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.

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