miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20
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Zixing Liu1, Kelly R. Smith1, Hung T. Khong2, Jingshan Huang3, Eun-Young Erin Ahn1, Ming Zhou4, Ming Tan1,5
1Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA
2Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA
3School of Computing, University of South Alabama, Mobile, AL, USA
4Cancer Research Institute, Central South University, Changsha, Hunan, China
5Department of Biochemistry & Molecular Biology, University of South Alabama, Mobile, AL, USA
Ming Zhou, email: firstname.lastname@example.org
Ming Tan, email: email@example.com
Keywords: T cell, lymphocytic leukemia, differentiation, miR-125b, A20
Received: January 26, 2016 Accepted: September 02, 2016 Published: September 14, 2016
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy. Although it has been reported that overexpression of miR-125b leads to T-ALL development, the underlying mechanisms of miR-125b action are still unclear. The goal of this study is to delineate the role of miR-125b in T-ALL development. We found that miR-125b is highly expressed in undifferentiated leukemic T cells (CD4-negative) while its expression is low in differentiated T cells (CD4-positive). Overexpression of miR-125b increased the CD4-negative population in T cells, whereas depletion of miR-125b by miR-125b-sponge decreased the CD4-negative cell population. We identified that A20 (TNFAIP3) is a direct target of miR-125b in T cells. Overexpression of miR-125b also increased glucose uptake and oxygen consumption in T cells through targeting A20. Furthermore, restoration of A20 in miR-125b-overexpressing cells decreased the CD4-negative population in T cell leukemia, and decreased glucose uptake and oxygen consumption to the basal level of T cells transfected with vector. In conclusion, our data demonstrate that miR-125b regulates differentiation and reprogramming of T cell glucose metabolism via targeting A20. Since both de-differentiation and dysregulated glucose metabolism contribute to the development of T-cell leukemia, these findings provide novel insights into the understanding and treatment of T-ALL.
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