Department of Hematology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shanxi Province; Department of Bone Marrow Transplantation, Harbin Hematological Cancer Institute, Harbin the First Hospital, Harbin 150010, People's Republic of China.
Department of Hematology, the First Hospital of Qiqihar, Qiqihar 150001, People's Republic of China.
BMB Rep. 2018 Sep;51(9):444-449. doi: 10.5483/bmbrep.2018.51.9.036.
Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significantly downregulated in AML tissues and cell lines. In addition, overexpression of miR-204 induced growth inhibition and apoptosis in AML cells, including AML5, HL-60, Kasumi-1 and U937 cells. Cell cycle analysis further confirmed an augmentation in theapoptotic subG1 population by miR-204 overexpression. Mechanistically, baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) was identified as a direct target of miR-204. Enforcing miR-204 expression increased the luciferase activity and expression of BIRC6, as well as p53 and Bax expression. Moreover, restoration of BIRC6 reversed the pro-apoptotic effects of miR-204 overexpression in AML cells. Taken together, this study demonstrates that miR-204 causes AML cell apoptosis by targeting BIRC6, suggesting miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease. [BMB Reports 2018; 51(9): 444-449].
急性髓系白血病（AML）是全世界最常见的血液系统恶性肿瘤之一。微小 RNA（miRNA）已被确定在多种癌症的发生和发展中发挥作用，包括 AML。虽然 microRNA-204（miR-204）在几种癌症中发挥抗肿瘤作用，但它在 AML 中的作用尚不清楚。在本研究中，我们评估了 AML 血液样本和细胞系中的 miR-204 表达。我们还研究了 miR-204 对 AML 细胞的细胞功能的影响及其作用的潜在机制。我们的结果表明，miR-204 在 AML 组织和细胞系中表达明显下调。此外，miR-204 的过表达诱导 AML 细胞，包括 AML5、HL-60、Kasumi-1 和 U937 细胞的生长抑制和凋亡。细胞周期分析进一步证实 miR-204 过表达导致凋亡亚 G1 群体增加。从机制上讲，杆状病毒抑制凋亡蛋白重复包含 6（BIRC6）被鉴定为 miR-204 的直接靶标。增强 miR-204 的表达增加了 BIRC6 的荧光素酶活性和表达，以及 p53 和 Bax 的表达。此外，BIRC6 的恢复逆转了 miR-204 过表达在 AML 细胞中的促凋亡作用。总之，这项研究表明，miR-204 通过靶向 BIRC6 导致 AML 细胞凋亡，表明 miR-204 在 AML 中可能发挥抗癌作用，并可作为该疾病治疗的新型生物标志物和治疗靶标。[BMB 报告 2018；51（9）：444-449]。
