笑对人生
(2022-08-31 21:18):
#paper Dynamic patterns of microRNA expression during acute myeloid leukemia state-transition. Sci Adv. 2022 Apr 22;8(16):eabj1664. doi: 10.1126/sciadv.abj1664.
miRNAs是一类长度为21nt的非编码RNA，自1993年首次发现以来，至今已将近30年。在机体内，miRNAs大多数扮演微调的角色。既往的研究已证明miRNAs能作为急性髓系白血病（AML）预后的生物标志物。Inv(16)是与急性髓系白血病密切相关的一种常见染色体易位，携带该变异的患者占总AML患者的5%。该白血病亚型的分子特征是染色体上的CBFB和MYH11基因的相互易位产生CBFB-MYH11融合基因。本研究利用敲入Cbfb-MYH11融合基因小鼠的PBMC，首次绘制AML从疾病开始到进展的动态miRNAs图谱，测序技术使用的是基于PAGE（聚丙烯酰胺凝胶电泳）进行片段筛选的miRNA-seq。研究将每只小鼠的 miRNA 转录组作为准电位中经历布朗运动的粒子，并分成两个稳态，受扰动的造血c1和AMLc2，这两个稳态由不稳定的过渡态（c3）隔开。进一步地将AML疾病由发生到进展划分为四个不同的事件，最终获得四个反映不同疾病进展的miRNAs集。基于先前来自相同小鼠模型PBMC的mRNA测序数据，研究证实了miRNA表达谱在描述疾病进展过程，与mRNA表达相比，具有一定相似性。更为重要的是，该研究发现mmu-miR-126a在疾病发展进程中表达逐渐上调，并与5个AML致病基因（Prkd1、Egfl7、Wt1、Kite和Cbfb-MYH11）的表达高度正相关。此外，还发现了先前未报道的，但与5个致病基因表达高度正相关的miRNAs，分别是mmu-miR-31 和 mmu-miR-340。
Dynamic patterns of microRNA expression during acute myeloid leukemia state-transition
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Abstract:
MicroRNAs (miRNAs) have been shown to hold prognostic value in acute myeloid leukemia (AML); however, the temporal dynamics of miRNA expression in AML are poorly understood. Using serial samples from a mouse model of AML to generate time-series miRNA sequencing data, we are the first to show that the miRNA transcriptome undergoes state-transition during AML initiation and progression. We modeled AML state-transition as a particle undergoing Brownian motion in a quasi-potential and validated the AML state-space and state-transition model to accurately predict time to AML in an independent cohort of mice. The critical points of the model provided a framework to align samples from mice that developed AML at different rates. Our mathematical approach allowed discovery of dynamic processes involved during AML development and, if translated to humans, has the potential to predict an individual's disease trajectory.
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