Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306,China; National Demonstration Center for Experimental Fisheries Science Education,Shanghai Ocean University, Shanghai, 201306,China.
Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306,China; National Demonstration Center for Experimental Fisheries Science Education,Shanghai Ocean University, Shanghai, 201306,China; Marine Biomedical Science and Technology Innovation Platform of Lin-gang Special Area, Shanghai, 201306, China.
Biochem Biophys Res Commun. 2024 Sep 10;724:150221. doi: 10.1016/j.bbrc.2024.150221. Epub 2024 Jun 6.
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.
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，但迄今为止，MYB 调节的机制仍不清楚。我们之前的研究确定了一种来自 MYB 基因座 -34kb 增强子的长非编码 RNA（lncRNA），它可以促进 MYB 的表达、人白血病细胞的增殖和迁移，因此被命名为 MY34UE-AS。然后，本研究鉴定并研究了与 MY34UE-AS 相互作用的伴侣蛋白。hnRNPA0 通过 RNA 下拉实验被鉴定为 MY34UE-AS 的结合伴侣，通过 RNA 免疫沉淀（RIP）进一步验证。hnRNPA0 主要通过其 RRM2 结构域与 MY34UE-AS 相互作用。hnRNPA0 的过表达上调了 MYB 并增加了 K562 细胞的增殖和迁移，而 hnRNPA0 的敲低则显示出相反的效果。挽救实验表明，MY34UE-AS 是 hnRNPA0 发挥上述功能所必需的。这些结果表明，hnRNPA0 通过与 MY34UE-AS 相互作用上调 MYB 表达参与白血病，表明 hnRNPA0/MY34UE-AS 轴可作为白血病治疗的潜在靶点。
