Oncotarget

Research Papers:

miRNA regulation of Tip110 expression and self-renewal and differentiation of human CD34+ hematopoietic cells

Ying Liu _, Xinxin Huang, Khalid A. Timani, Hal E. Broxmeyer and Johnny J. He

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Oncotarget. 2018; 9:4823-4832. https://doi.org/10.18632/oncotarget.23572

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Abstract

Ying Liu1, Xinxin Huang2, Khalid A. Timani1, Hal E. Broxmeyer2 and Johnny J. He1

1Department of Microbiology, Immunology and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA

2Department of Microbiology and Immunology, Indiana University, Indianapolis, IN 46202, USA

Correspondence to:

Ying Liu, email: ying.liu@unthsc.edu

Keywords: hematopoiesis; CD34+; miRNA; 3′UTR; ceRNA

Received: October 05, 2017     Accepted: December 14, 2017     Published: December 21, 2017

ABSTRACT

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.


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