Work

miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20

Year: 2016

Type: article

Abstract: // Zixing Liu 1 , Kelly R. Smith 1 , Hung T. Khong 2 , Jingshan Huang 3 , Eun-Young Erin Ahn 1 , Ming Zhou 4 , Ming Tan 1, 5 1 Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA 2 Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA 3 School of Computing, University of South Alabama, Mobile, AL, USA 4 Cancer Research Institute, Central South University, Changsha, Hunan, China 5 Department of Biochemistry & Molecular Biology, University of South Alabama, Mobile, AL, USA Correspondence to: Ming Zhou, email: [email protected] Ming Tan, email: [email protected] Keywords: T cell, lymphocytic leukemia, differentiation, miR-125b, A20 Received: January 26, 2016 Accepted: September 02, 2016 Published: September 14, 2016 ABSTRACT 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.12018