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

Sırma E., Emrence Z., Abacı N., Sariman M., Salman B., Ekmekci C., ...More

Turkish Journal of Hematology, vol.37, no.4, pp.226-233, 2020 (SCI-Expanded, Scopus, TRDizin) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 4
  • Publication Date: 2020
  • Doi Number: 10.4274/tjh.galenos.2020.2020.0144
  • Journal Name: Turkish Journal of Hematology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.226-233
  • Keywords: T-cell acute lymphoblastic leukemia, p53, DHRS2, LEF1, siRNA, ACUTE LYMPHOBLASTIC-LEUKEMIA, FACTOR-I LEF1, CHRONIC LYMPHOCYTIC-LEUKEMIA, FAVORABLE PROGNOSTIC-FACTOR, STROMAL TUMORS, CHROMOSOME 14, STEM-CELLS, C-MYC, NOTCH1, MUTATIONS
  • Istanbul University Affiliated: Yes

Abstract

Objective: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressivedisease resulting from the accumulation of genetic changes that affectthe development of T-cells. The precise role of lymphoid enhancerbinding factor 1 (LEF1) in T-ALL has been controversial since bothoverexpression and inactivating LEF1 mutations have been reportedto date. Here, we investigate the potential gene targets of LEF1 in theJurkat 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 comparedthe gene expression levels in the LEF1 knockdown cells with nontargeting siRNA-transfected and non-transfected cells by employingmicroarray analysis.Results: We identified DHRS2, a tumor suppressor gene, as the mostsignificantly downregulated gene in LEF1 knockdown cells, and wefurther confirmed its downregulation by real-time quantitativepolymerase chain reaction (qRT-PCR) in mRNA and at protein level bywestern blotting.Conclusion: Our results revealed that DHRS2 is positively regulated byLEF1 in Jurkat cells, which indicates the capability of LEF1 as a tumorsuppressor and, together with previous reports, suggests that LEF1exhibits a regulatory role in T-ALL via not only its oncogenic targetsbut also tumor suppressor genes.