Abstract：
MYB is a key regulator of hematopoiesis and erythropoiesis, and dysregulation of MYB is closely involved in the development of leukemia, however the mechanism of MYB regulation remains still unclear so far. Our previous study identified a long noncoding RNA (lncRNA) derived from the -34 kb enhancer of the MYB locus, which can promote MYB expression, the proliferation and migration of human leukemia cells, and is therefore termed MY34UE-AS. Then the interacting partner proteins of MY34UE-AS were identified and studied in the present study. hnRNPA0 was identified as a binding partner of MY34UE-AS through RNA pulldown assay, which was further validated through RNA immunoprecipitation (RIP). hnRNPA0 interacted with MY34UE-AS mainly through its RRM2 domain. hnRNPA0 overexpression upregulated MYB and increased the proliferation and migration of K562 cells, whereas hnRNPA0 knockdown showed opposite effects. Rescue experiments showed MY34UE-AS was required for above mentioned functions of hnRNPA0. These results reveal that hnRNPA0 is involved in leukemia through upregulating MYB expression by interacting with MY34UE-AS, suggesting that the hnRNPA0/MY34UE-AS axis could serve as a potential target for leukemia treatment.
摘要：
MYB是造血和红细胞生成的关键调节因子,MYB的失调与白血病的发展密切相关，然而，到目前为止，MYB调控的机制仍不清楚。我们之前的研究发现了一个来自MYB基因座-34kb增强子的长的非编码RNA(lncRNA),可以促进MYB的表达，人类白血病细胞的增殖和迁移，因此被称为MY34UE-AS。然后在本研究中鉴定并研究了MY34UE-AS的相互作用伴侣蛋白。hnRNPA0通过RNA下拉测定被鉴定为MY34UE-AS的结合配偶体，通过RNA免疫沉淀（RIP）进一步验证。hnRNPA0主要通过其RRM2域与MY34UE-AS相互作用。hnRNPA0过表达上调MYB并增加K562细胞的增殖和迁移,而hnRNPA0敲低显示出相反的效果。抢救实验表明，hnRNPA0的上述功能需要MY34UE-AS。这些结果表明，hnRNPA0通过与MY34UE-AS相互作用上调MYB表达而参与白血病，提示hnRNPA0/MY34UE-AS轴可作为白血病治疗的潜在靶点。
