miR-125a 通过靶向 ErbB 通路调控急性髓系白血病细胞周期、增殖和凋亡。
miR-125a regulates cell cycle, proliferation, and apoptosis by targeting the ErbB pathway in acute myeloid leukemia.
机构信息
The Graduate School of Biomedical Sciences, University of Maine, Orono, ME, USA; Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
出版信息
Leuk Res. 2014 Mar;38(3):402-10. doi: 10.1016/j.leukres.2013.12.021. Epub 2014 Jan 8.
Abstract
microRNA profiling of acute myeloid leukemia patient samples identified miR-125a as being decreased. Current literature has investigated miR-125a's role in normal hematopoiesis but not within acute myeloid leukemia. Analysis of the upstream region of miR-125a identified several CpG islands. Both precursor and mature miR-125a increased in response to a de-methylating agent, Decitabine. Profiling revealed the ErbB pathway as significantly decreased with ectopic miR-125a. Either ectopic expression of miR-125a or inhibition of ErbB via Mubritinib resulted in inhibition of cell cycle proliferation and progression with enhanced apoptosis revealing ErbB inhibitors as potential novel therapeutic agents for treating miR-125a-low AML.
摘要
对急性髓系白血病患者样本的 microRNA 谱分析发现 miR-125a 减少。目前的文献已经研究了 miR-125a 在正常造血过程中的作用，但没有研究其在急性髓系白血病中的作用。miR-125a 上游区域的分析确定了几个 CpG 岛。前体和成熟的 miR-125a 都对去甲基化剂地西他滨有反应而增加。分析显示，外源性 miR-125a 可显著降低 ErbB 通路。外源性表达 miR-125a 或通过 Mubritinib 抑制 ErbB 均可抑制细胞周期增殖和进展，促进细胞凋亡，表明 ErbB 抑制剂可能是治疗 miR-125a 低表达 AML 的新型治疗药物。
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