Liu Ying, Huang Xinxin, Timani Khalid A, Broxmeyer Hal E, He Johnny J
Department of Microbiology, Immunology and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Department of Microbiology and Immunology, Indiana University, Indianapolis, IN 46202, USA.
Oncotarget. 2017 Dec 21;9(4):4823-4832. doi: 10.18632/oncotarget.23572. eCollection 2018 Jan 12.
Tip110 expression regulates hematopoiesis, but the regulatory mechanisms during hematopoiesis are not fully understood. There are a number of putative microRNA (miRNA) binding sites identified within the Tip110 3' untranslated region (3'UTR). In this study, we determined the relationship among Tip110 miRNA, Tip110 expression and self-renewal and differentiation of human CD34+ hematopoietic cells. Using a Tip110 3UTR-based reporter gene assay, 11 miRNA showed the specific activity toward the Tip110 3'UTR and down-regulated constitutive Tip110 mRNA expression. When human cord blood CD34+ cells were differentiated, Tip110 mRNA expression showed significant decreases. Concurrently, five miRNA showed significant increases, five miRNA showed significant decreases, and one miRNA remained unchanged. To further assess the roles of miRNA in Tip110 expression and self-renewal and differentiation of human CD34+ hematopoietic cells, human cord blood CD34+ cells were transduced to express the full-length Tip110 3'UTR RNA. Expression of the Tip110 3'UTR RNA led to significant increases of Tip110 mRNA, and the number of hematopoietic stem cells and progenitor cells. Taken together, these results show important roles of Tip110 miRNA in Tip110 expression control and Tip110 regulation of hematopoiesis and offer a possibility of using Tip110 miRNA or 3'UTR as a strategy to maintain human CD34+ hematopoietic cells.
Tip110表达调控造血过程，但其在造血过程中的调控机制尚未完全明确。在Tip110的3'非翻译区（3'UTR）内已鉴定出多个假定的微小RNA（miRNA）结合位点。在本研究中，我们确定了Tip110 miRNA、Tip110表达以及人CD34+造血细胞自我更新和分化之间的关系。使用基于Tip110 3UTR的报告基因检测，11种miRNA对Tip110 3'UTR表现出特异性活性，并下调Tip110组成型mRNA表达。当人脐带血CD34+细胞分化时，Tip110 mRNA表达显著下降。同时，5种miRNA显著增加，5种miRNA显著减少，1种miRNA保持不变。为进一步评估miRNA在Tip110表达以及人CD34+造血细胞自我更新和分化中的作用，将人脐带血CD34+细胞转导以表达全长Tip110 3'UTR RNA。Tip110 3'UTR RNA的表达导致Tip110 mRNA以及造血干细胞和祖细胞数量显著增加。综上所述，这些结果表明Tip110 miRNA在Tip110表达控制以及Tip110对造血的调控中发挥重要作用，并为使用Tip110 miRNA或3'UTR作为维持人CD34+造血细胞的策略提供了可能性。
