LEF1 Induces DHRS2 Gene Expression in Human Acute Leukemia Jurkat T-Cells

Abstract

Objective: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease resulting from the accumulation of genetic changes that affect the development of T-cells. The precise role of lymphoid enhancerbinding factor 1 (LEF1) in T-ALL has been controversial since both overexpression and inactivating LEF1 mutations have been reported to date. Here, we investigate the potential gene targets of LEF1 in the Jurkat human T-cell leukemia cell line. Materials and Methods: We used small interfering RNA (siRNA) technology to knock down LEF1 in Jurkat cells and then compared the gene expression levels in the LEF1 knockdown cells with nontargeting siRNA-transfected and non-transfected cells by employing microarray analysis. Results: We identified DHRS2, a tumor suppressor gene, as the most significantly downregulated gene in LEF1 knockdown cells, and we further confirmed its downregulation by real-time quantitative polymerase chain reaction (qRT-PCR) in mRNA and at protein level by western blotting. Conclusion: Our results revealed that DHRS2 is positively regulated by LEF1 in Jurkat cells, which indicates the capability of LEF1 as a tumor suppressor and, together with previous reports, suggests that LEF1 exhibits a regulatory role in T-ALL via not only its oncogenic targets but also tumor suppressor genes.

Keywords

• t-cell acute lymphoblastic leukemia
• p53
• dhrs2
• lef1
• sirna