Department of Hematology, Yidu Central Hospital of Weifang, Weifang, Shandong 262550, P.R. China.
Department of Clinical Laboratory, Jinan Hospital for Infectious Diseases, Jinan, Shandong 250021, P.R. China.
Mol Med Rep. 2018 Dec;18(6):5261-5269. doi: 10.3892/mmr.2018.9552. Epub 2018 Oct 10.
In recent decades, microRNAs (miRNAs) have been considered novel gene regulators. Dysregulated miRNAs serve crucial roles in the formation and progression of acute myeloid leukaemia (AML). Therefore, the roles of differentially expressed miRNAs in AML require extensive investigation to obtain insight into the treatment of patients with AML. The present study demonstrated significant miR‑339‑5p downregulation in AML samples and cell lines. miR‑339‑5p overexpression attenuated AML cell proliferation by inducing cell cycle arrest and promoting cell apoptosis. Additionally, sex‑determining region Y‑related high‑mobility group box 4 (SOX4) was identified as a direct target gene of miR‑339‑5p in AML. Furthermore, SOX4 expression was significantly upregulated in AML samples; this upregulation was inversely correlated with the expression levels of miR‑339‑5p. Additionally, a series of rescue experiments demonstrated that SOX4 resumption reversed the effects of miR‑339‑5p overexpression on cell proliferation, cycle status and apoptosis of AML. In conclusion, miR‑339‑5p may serve its antiproliferative role in AML by directly targeting SOX4, which suggests that miR‑339‑5p may be considered an effective novel therapeutic target for treating patients with such an aggressive haematological malignancy.
在最近几十年中,microRNAs (miRNAs) 被认为是新型的基因调节剂。失调的 miRNAs 在急性髓系白血病 (AML) 的形成和进展中起着至关重要的作用。因此,需要广泛研究差异表达的 miRNAs 在 AML 中的作用,以深入了解 AML 患者的治疗方法。本研究表明,miR-339-5p 在 AML 样本和细胞系中表达显著下调。miR-339-5p 过表达通过诱导细胞周期停滞和促进细胞凋亡来抑制 AML 细胞增殖。此外,性别决定区 Y 相关高迁移率族蛋白盒 4 (SOX4) 被鉴定为 AML 中 miR-339-5p 的直接靶基因。此外,AML 样本中 SOX4 的表达显著上调;这种上调与 miR-339-5p 的表达水平呈负相关。此外,一系列挽救实验表明,SOX4 的恢复逆转了 miR-339-5p 过表达对 AML 细胞增殖、周期状态和凋亡的影响。综上所述,miR-339-5p 可能通过直接靶向 SOX4 发挥其在 AML 中的抗增殖作用,这表明 miR-339-5p 可能被认为是治疗这种侵袭性血液恶性肿瘤患者的有效新型治疗靶点。