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靶向 Smad4 将 microRNA-146a 与急性早幼粒细胞白血病细胞系维甲酸诱导过程中的 TGF-β 通路联系起来。

Targeting Smad4 links microRNA-146a to the TGF-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line.

机构信息

Department of Hematology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People's Republic of China.

出版信息

Int J Hematol. 2010 Jul;92(1):129-35. doi: 10.1007/s12185-010-0626-5. Epub 2010 Jun 25.

DOI:10.1007/s12185-010-0626-5
PMID:20577838
Abstract

The expression pattern of microRNAs (miRNAs) and their potential target genes were investigated in acute promyelocytic leukemia (APL) cell line NB4 cells during all-trans-retinoid acid (ATRA) treatment by using a miRNA microarrays platform and real-time quantitative PCR (RTQ-PCR). MiR-146a as one of the miRNAs down-regulated by ATRA during APL differentiation was identified. Direct interaction between miR146a and its predictive target gene Smad4 were confirmed by Luciferase assay. Down-regulation of miR-146a and upregulation of Smad4 at protein levels were demonstrated. These data suggested that miR-146a might influence proliferation of APL cells through TGF-beta1/Smad signal transduction pathway during ATRA induction.

摘要

采用 miRNA 微阵列平台和实时定量 PCR(RTQ-PCR)技术,研究了全反式维甲酸(ATRA)治疗急性早幼粒细胞白血病(APL)细胞系 NB4 细胞过程中 microRNAs(miRNAs)的表达模式及其潜在靶基因。鉴定出 miR-146a 是 ATRA 诱导 APL 分化过程中下调的 miRNAs 之一。通过荧光素酶测定证实了 miR146a 与其预测靶基因 Smad4 之间的直接相互作用。证实了 miR-146a 在蛋白质水平下调和 Smad4 上调。这些数据表明,miR-146a 可能通过 ATRA 诱导时 TGF-β1/Smad 信号转导通路影响 APL 细胞的增殖。

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