Kuang Xingyi, Wei Chunmei, Zhang Tao, Yang Zesong, Chi Jianxiang, Wang Li
Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
The Center for the Study of Haematological Malignancies, 2032 Nicosia, Cyprus.
Int J Oncol. 2016 Nov;49(5):1921-1930. doi: 10.3892/ijo.2016.3689. Epub 2016 Sep 13.
miR-378 has been proven to inhibit cell growth, migration and invasion in different types of cancers. In this study, we found that miR-378 was commonly downregulated in the bone marrow cells obtained from myelodysplastic syndrome (MDS) patients. We further investigated the role of miR-378 in the proliferation and apoptosis of SKM-1 cells, an acute myeloid leukemia cell line established in the leukemic phase during the progression of MDS to AML (MDS/AML). Results indicated that overexpression of miR-378 in SKM-1 cells interfered with proliferation via inducing apoptosis and G0/G1-phase cell cycle arrest, and suppressive effect of miR-378 on MDS/AML cells may be mediated partly through Bcl-w and CDC40. Moreover, apoptosis induced by miR-378 correlated with increased expression of Bax and activation of caspase-3, -8 and -9. Taken together, our data support a critical role for miR-378 in the pathogenesis of MDS and provide a novel therapeutic target in this complex disease.
已证实miR-378可抑制不同类型癌症中的细胞生长、迁移和侵袭。在本研究中，我们发现miR-378在骨髓增生异常综合征（MDS）患者的骨髓细胞中普遍下调。我们进一步研究了miR-378在SKM-1细胞增殖和凋亡中的作用，SKM-1细胞是一种在MDS进展为急性髓系白血病（AML，即MDS/AML）的白血病阶段建立的急性髓系白血病细胞系。结果表明，SKM-1细胞中miR-378的过表达通过诱导凋亡和G0/G1期细胞周期阻滞来干扰增殖，并且miR-378对MDS/AML细胞的抑制作用可能部分通过Bcl-w和CDC40介导。此外，miR-378诱导的凋亡与Bax表达增加以及caspase-3、-8和-9的激活相关。综上所述，我们的数据支持miR-378在MDS发病机制中起关键作用，并为这种复杂疾病提供了一个新的治疗靶点。
