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

Academic Article


  • 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.
  • Published In

  • Oncotarget  Journal
  • Keywords

  • A20, T cell, differentiation, lymphocytic leukemia, miR-125b, CD4-Positive T-Lymphocytes, Cell Differentiation, Cellular Reprogramming, Energy Metabolism, Gene Expression Regulation, Leukemic, Glucose, Humans, Jurkat Cells, MicroRNAs, Oxygen Consumption, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Signal Transduction, Transfection, Tumor Necrosis Factor alpha-Induced Protein 3
  • Digital Object Identifier (doi)

    Author List

  • Liu Z; Smith KR; Khong HT; Huang J; Ahn E-YE; Zhou M; Tan M
  • Start Page

  • 78667
  • End Page

  • 78679
  • Volume

  • 7
  • Issue

  • 48