miR-603通过向TrkB来促进细胞增殖和分化,在急性前兆细胞白血病中发挥作用
Huibo Li1, Jinxiao Hou1,2, Yueyue Fu1
1Department of Hematology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China.
Annals of hematology
|September 19, 2023
概括
在复发性急性肌肉细胞白血病 (APL) 中,microRNA-603 (miR-603) 的下调. 较低的miR-603水平与增加的热胺相关激酶B (TrkB) 相相关,促进APL细胞增殖和抑制细胞亡,这表明一种新的治疗点.
科学领域:
- 血液学 血液学 血液学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 三氧化物 (ATO) 有效治疗急性肌肉细胞白血病 (APL).
- 在APL中,ATO耐药性和复发可能与PML::RARA突变有关,但有些复发患者缺乏这些突变.
- 显著的微RNA (miRNA) 表达特征可能是APL中ATO耐药性和复发的基础.
研究的目的:
- 调查新诊断的与复发APL的微分miRNA表达.
- 为了识别特定的miRNA及其参与APL复发的点.
- 探索miR-603/TrkB轴在复发APL中的治疗潜力.
主要方法:
- 微阵列分析用于比较APL患者样本中的miRNA表达.
- 定量PCR和西布洛特测试以评估miR-603和与热胺相关的B激酶 (TrkB) 的表达.
- 在APL细胞系中进行MTT测定,流细胞计以分析细胞增殖,细胞亡,细胞周期和CD11b表达.
主要成果:
- 微阵列分析揭示了新诊断和复发APL之间不同的miRNA表达模式.
- 在复发APL患者中,miR-603显著下调.
- miR-603直接向TrkB,降低其表达,随后增加APL细胞的增殖,同时抑制细胞亡.
结论:
- 该miR-603/TrkB信号通路在复发APL的发病过程中起着至关重要的作用.
- 通过促进细胞增殖和存活,对miR-603的降低调节有助于APL复发.
- 针对miR-603/TrkB轴为复发APL提供了一个有希望的治疗策略.
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