Department of Oncology, The First People's Hospital of Lianyungang, No. 6 Zhenhua Earth Road, Lianyungang City, 222061, Jiangsu Province, People's Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Jan;394(1):177-187. doi: 10.1007/s00210-020-01892-4. Epub 2020 May 29.
Acute myeloid leukemia (AML) is a widely prevalent disease worldwide and poses a large threat to public health. Previous studies have shown that AML is associated with cytogenetic heterogeneity, complex subtypes, and different therapeutic approaches. In this study, we found that miR-486 was upregulated in AML using both The Cancer Genome Atlas (TCGA) database and patient tissues. After knockdown of miR-486 by short hairpin RNA (shRNA), we discovered that miR-486 was required for cell proliferation. Through miRNA profile analysis and a dual-luciferase reporter assay, suppressor of cytokine signaling 2 (SOCS2) was identified as a direct target of miR-486. Therefore, by silencing SOCS2, a negative regulator of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, miR-486 enhanced JAK-STAT3 activity and promoted cell proliferation. The miR-486-SOCS2-STAT3 proliferation axis is therefore involved in the pathogenesis of AML, providing a novel molecular mechanism and diagnostic and therapeutic clues for AML.
急性髓细胞白血病（AML）是一种广泛存在于世界各地的疾病，对公众健康构成了巨大威胁。先前的研究表明，AML 与细胞遗传学异质性、复杂亚型和不同的治疗方法有关。在这项研究中，我们使用癌症基因组图谱（TCGA）数据库和患者组织发现 miR-486 在 AML 中上调。通过短发夹 RNA（shRNA）敲低 miR-486 后，我们发现 miR-486 是细胞增殖所必需的。通过 miRNA 谱分析和双荧光素酶报告基因检测，发现抑制细胞因子信号 2（SOCS2）是 miR-486 的直接靶标。因此，通过沉默 SOCS2，一种 Janus 激酶（JAK）-信号转导和转录激活因子（STAT）通路的负调节剂，miR-486 增强了 JAK-STAT3 活性并促进了细胞增殖。因此，miR-486-SOCS2-STAT3 增殖轴参与 AML 的发病机制，为 AML 提供了新的分子机制和诊断及治疗线索。
