Department of Medicine, Department of Veterans Affairs Medical Center and University of California, San Francisco, CA 94143, USA.
Nucleic Acids Res. 2010 Sep;38(16):5472-8. doi: 10.1093/nar/gkq337. Epub 2010 May 5.
HOXA9-mediated up-regulation of miR-155 was noted during an array-based analysis of microRNA expression in Hoxa9(-/-)bone marrow (BM) cells. HOXA9 induction of miR-155 was confirmed in these samples, as well as in wild-type versus Hoxa9-deficient marrow, using northern analysis and qRT-PCR. Infection of wild-type BM with HOXA9 expressing or GFP(+) control virus further confirmed HOXA9-mediated regulation of miR-155. miR-155 expression paralleled Hoxa9 mRNA expression in fractionated BM progenitors, being highest in the stem cell enriched pools. HOXA9 capacity to induce myeloid colony formation was blunted in miR-155-deficient BM cells, indicating that miR-155 is a downstream mediator of HOXA9 function in blood cells. Pu.1, an important regulator of myelopoiesis, was identified as a putative down stream target for miR-155. Although miR-155 was shown to down-regulate the Pu.1 protein, HOXA9 did not appear to modulate Pu.1 expression in murine BM cells.
在基于微阵列的 Hoxa9(-/-)骨髓 (BM) 细胞 microRNA 表达分析中，注意到 HOXA9 介导的 miR-155 上调。在这些样本中以及在野生型与 Hoxa9 缺失型骨髓中，通过 northern 分析和 qRT-PCR 证实了 HOXA9 诱导 miR-155。用表达 HOXA9 的或 GFP(+)对照病毒感染野生型 BM 进一步证实了 HOXA9 对 miR-155 的调节。miR-155 表达与 BM 祖细胞的分馏呈平行关系，在干细胞富集池中最高。在 miR-155 缺失型 BM 细胞中，HOXA9 诱导髓样集落形成的能力减弱，表明 miR-155 是 HOXA9 在血细胞中功能的下游介质。Pu.1，一种重要的髓系生成调节剂，被鉴定为 miR-155 的一个假定下游靶标。尽管 miR-155 被证明下调 Pu.1 蛋白，但 HOXA9 似乎并未在小鼠 BM 细胞中调节 Pu.1 表达。
