Xu Lan, Zhong Hua, Wan Haixia, Chen Fang-yuan, Zhong Jihua, Xiao Fei, Liu Jia, Shen Lijing
Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Dis Markers. 2014;2014:150604. doi: 10.1155/2014/150604. Epub 2014 Aug 5.
Although the curative rate for acute promyelocytic leukemia (APL) has been improved over decades, long-term prognosis is still poor. The genetic pathways that regulated cell lineage fate during the development of APL remain unclear.
We investigated the correlations of miR-146a expression with its target gene Smad4 and the biological behaviors of NB4 cells. We also analyzed their expression in clinical samples from APL patients.
miR-146a influenced apoptosis and proliferation in NB4 cells. miR-146a influenced endogenous Smad4 protein levels in APL cells. miR-146a expression levels were positively correlated with white cell counts and PML/RARα fusion protein expression. miR-146a expression levels were negatively correlated with Smad4 protein and the helper T cell (Th)/the suppressor T cell (Ts) ratio in these patients.
These findings indicated that miR-146a played an important role in the development of APL in part through the repression on Smad4 protein expression. miR-146a functioned as an oncogene and may be a novel prognostic biomarker in APL.
尽管数十年来急性早幼粒细胞白血病(APL)的治愈率有所提高,但长期预后仍然较差。APL发生发展过程中调控细胞谱系命运的遗传通路仍不清楚。
我们研究了miR-146a表达与其靶基因Smad4以及NB4细胞生物学行为之间的相关性。我们还分析了它们在APL患者临床样本中的表达情况。
miR-146a影响NB4细胞的凋亡和增殖。miR-146a影响APL细胞中内源性Smad4蛋白水平。miR-146a表达水平与白细胞计数和PML/RARα融合蛋白表达呈正相关。miR-146a表达水平与这些患者的Smad4蛋白以及辅助性T细胞(Th)/抑制性T细胞(Ts)比值呈负相关。
这些发现表明,miR-146a在APL发生发展中发挥重要作用,部分是通过抑制Smad4蛋白表达实现的。miR-146a起到癌基因的作用,可能是APL中一种新的预后生物标志物。