Ying Xiaoyang, Zhang Wanggang, Fang Meiyun, Zhang Weijun, Wang Chenchen, Han Li
Department of Clinical Hematology, Affiliated No. 2 Hospital School of Medicine, Xi'an Jiaotong University, China.
Department of Hematology, Affiliated Zhongshan Hospital of Dalian University, China.
J Cell Biochem. 2019 Feb;120(2):1620-1629. doi: 10.1002/jcb.27461. Epub 2018 Oct 2.
Acute myeloid leukemia (AML) is a malignant clonal hematopoietic disease, which is caused by hematopoietic stem cell abnormalities. Epigenetic regulation, especially of microRNAs (miRNAs), mostly results from external or environmental effects and is critical to AML. In this study, for the first time, we report that decreased expression of miR-345-5p facilitates the proliferation of leukemia cells in AML. Further study demonstrated that AKT1/2 was the target of miR-345-5p and was responsible for the dysregulation of leukemia cell proliferation and apoptosis. Inhibition of AKT1/2 ameliorated this malignant effect, which provides new insight into AML diagnosis, treatment, prognosis, and next-step translational investigations.
急性髓系白血病(AML)是一种恶性克隆性造血疾病,由造血干细胞异常引起。表观遗传调控,尤其是微小RNA(miRNA)的调控,主要源于外部或环境影响,对AML至关重要。在本研究中,我们首次报道miR-345-5p表达降低促进了AML中白血病细胞的增殖。进一步研究表明,AKT1/2是miR-345-5p的靶标,并且与白血病细胞增殖和凋亡的失调有关。抑制AKT1/2可改善这种恶性效应,这为AML的诊断、治疗、预后及下一步转化研究提供了新的见解。